Sympathetic and parasympathetic nervous system. Sympathetic and parasympathetic divisions of the autonomic nervous system: what are they? Angiotensin type I receptor antagonists

What is the autonomic nervous system?

The autonomic nervous system (ANS) is the involuntary part of the nervous system. It consists of autonomic neurons that conduct impulses from the central nervous system (brain and/or spinal cord), to glands, smooth muscles and to the heart. ANS neurons are responsible for regulating the secretions of certain glands (eg, salivary glands), regulating heart rate and peristalsis (contraction of smooth muscles in the digestive tract), as well as other functions.

The role of the ANS

The role of the ANS is to constantly regulate the functions of organs and organ systems, in accordance with internal and external stimuli. The ANS helps maintain homeostasis (regulation of the internal environment) by coordinating various functions such as hormone secretion, circulation, respiration, digestion, and elimination. The ANS always functions unconsciously; we do not know which of the important tasks it performs every minute of every day.
The ANS is divided into two subsystems, the SNS (sympathetic nervous system) and the PNS (parasympathetic nervous system).

Sympathetic Nervous System (SNS) – triggers what is commonly known as the “fight or flight” response

Sympathetic neurons usually belong to the peripheral nervous system, although some sympathetic neurons are located in the CNS (central nervous system)

Sympathetic neurons in the CNS (spinal cord) communicate with peripheral sympathetic neurons through a series of sympathetic nerve cells in the body known as ganglia

Through chemical synapses within the ganglia, sympathetic neurons attach to peripheral sympathetic neurons (for this reason, the terms "presynaptic" and "postsynaptic" are used to refer to spinal cord sympathetic neurons and peripheral sympathetic neurons, respectively)

Presynaptic neurons release acetylcholine at synapses within the sympathetic ganglia. Acetylcholine (ACh) is a chemical messenger that binds nicotinic acetylcholine receptors in postsynaptic neurons

Postsynaptic neurons release norepinephrine (NA) in response to this stimulus

Continued arousal response may cause adrenaline to be released from the adrenal glands (particularly the adrenal medulla)

Once released, norepinephrine and epinephrine bind to adrenergic receptors in various tissues, resulting in the characteristic "fight or flight" effect.

The following effects occur as a result of activation of adrenergic receptors:

Increased sweating
weakening of peristalsis
increase in heart rate (increase in conduction velocity, decrease in refractory period)
dilated pupils
increased blood pressure (increased heart rate to relax and fill up)

Parasympathetic Nervous System (PNS) – The PNS is sometimes referred to as the “rest and digest” system. In general, the PNS acts in the opposite direction to the SNS, eliminating the effects of the fight-or-flight response. However, it is more correct to say that the SNS and PNS complement each other.

The PNS uses acetylcholine as its main neurotransmitter
When stimulated, presynaptic nerve endings release acetylcholine (ACh) into the ganglion
ACh, in turn, acts on nicotinic receptors of postsynaptic neurons
postsynaptic nerves then release acetylcholine to stimulate muscarinic receptors in the target organ

The following effects occur as a result of activation of the PNS:

Decreased sweating
increased peristalsis
decreased heart rate (decreased conduction velocity, increased refractory period)
constriction of the pupil
lowering blood pressure (lowering the number of times the heart beats to relax and fill up)

Conductors of the SNS and PNS

The autonomic nervous system releases chemical conductors to influence its target organs. The most common are norepinephrine (NA) and acetylcholine (AC). All presynaptic neurons use ACh as a neurotransmitter. ACh also releases some sympathetic postsynaptic neurons and all parasympathetic postsynaptic neurons. The SNS uses NA as the basis of a postsynaptic chemical messenger. NA and ACh are the most well-known mediators of the ANS. In addition to neurotransmitters, some vasoactive substances are released by automatic postsynaptic neurons that bind to receptors on target cells and affect the target organ.

How is SNS conduction carried out?

In the sympathetic nervous system, catecholamines (norepinephrine, adrenaline) act on specific receptors located on the cell surface of target organs. These receptors are called adrenergic receptors.

Alpha-1 receptors exert their effect on smooth muscle, mainly through contraction. Effects may include contraction of arteries and veins, decreased mobility in the gastrointestinal tract (gastrointestinal tract), and constriction of the pupil. Alpha-1 receptors are usually located postsynaptically.

Alpha 2 receptors bind epinephrine and norepinephrine, thereby to some extent reducing the influence of alpha 1 receptors. However, alpha 2 receptors have several independent specific functions, including vasoconstriction. Functions may include coronary artery contraction, smooth muscle contraction, venous contraction, decreased intestinal motility, and inhibition of insulin release.

Beta-1 receptors exert their effects primarily on the heart, causing an increase in cardiac output, number of contractions and an increase in cardiac conduction, which leads to an increase in heart rate. Also stimulates the salivary glands.

Beta-2 receptors exert their effects mainly on skeletal and cardiac muscles. They increase the speed of muscle contraction and also dilate blood vessels. The receptors are stimulated by the circulation of neurotransmitters (catecholamines).

How does PNS conduction occur?

As already mentioned, acetylcholine is the main neurotransmitter of the PNS. Acetylcholine acts on cholinergic receptors known as muscarinic and nicotinic receptors. Muscarinic receptors exert their influence on the heart. There are two main muscarinic receptors:

M2 receptors are located in the very center, M2 receptors act on acetylcholine, stimulation of these receptors causes the heart to slow down (lowering the heart rate and increasing refractoriness).

M3 receptors are located throughout the body, activation leads to an increase in the synthesis of nitric oxide, which leads to relaxation of cardiac smooth muscle cells.

How is the autonomic nervous system organized?

As stated earlier, the autonomic nervous system is divided into two separate divisions: the sympathetic nervous system and the parasympathetic nervous system. It is important to understand how these two systems function in order to determine how they affect the body, keeping in mind that both systems work in synergy to maintain homeostasis in the body.
Both the sympathetic and parasympathetic nerves release neurotransmitters, primarily norepinephrine and epinephrine for the sympathetic nervous system, and acetylcholine for the parasympathetic nervous system.
These neurotransmitters (also called catecholamines) transmit nerve signals through the gaps created (synapses) when the nerve connects with other nerves, cells, or organs. Neurotransmitters then applied to either sympathetic receptor sites or parasympathetic receptors on the target organ exert their effect. This is a simplified version of the functions of the autonomic nervous system.

How is the autonomic nervous system controlled?

The ANS is not under conscious control. There are several centers that play a role in the control of the ANS:

Cerebral Cortex – Areas of the cerebral cortex control homeostasis by regulating the SNS, PNS, and hypothalamus.

Limbic System – The limbic system consists of the hypothalamus, amygdala, hippocampus and other nearby components. These structures lie on both sides of the thalamus, just below the brain.

The hypothalamus is the subthalamic region of the diencephalon, which controls the ANS. The hypothalamic region includes the parasympathetic vagus nuclei, as well as a group of cells that lead to the sympathetic system in the spinal cord. By interacting with these systems, the hypothalamus controls digestion, heart rate, sweating and other functions.

Stem Brain – The brain stem acts as a connection between the spinal cord and the brain. Sensory and motor neurons travel through the brainstem to carry messages between the brain and spinal cord. The brainstem controls many of the autonomic functions of the PNS, including breathing, heart rate, and blood pressure.

Spinal Cord – There are two chains of ganglia on either side of the spinal cord. The outer circuits are formed by the parasympathetic nervous system, while the circuits close to the spinal cord form the sympathetic element.

What are the receptors of the autonomic nervous system?

Afferent neurons, the dendrites of neurons that have receptor properties, are highly specialized, receiving only certain types of stimuli. We do not consciously feel impulses from these receptors (with the possible exception of pain). There are numerous sensory receptors:

Photoreceptors - respond to light
thermoreceptors - respond to changes in temperature
Mechanoreceptors – respond to stretch and pressure (blood pressure or touch)
Chemoreceptors - respond to changes in the body's internal chemistry (i.e., O2, CO2), dissolved chemicals, sense of taste and smell
Nociceptors - respond to various stimuli associated with tissue damage (the brain interprets pain)

Autonomic (visceral) motor neurons synapse on neurons located in the ganglia of the sympathetic and parasympathetic nervous system, directly innervating muscles and some glands. Thus, we can say that visceral motor neurons indirectly innervate the smooth muscles of the arteries and cardiac muscle. Autonomic motor neurons operate by increasing SNS or decreasing PNS activity in target tissues. In addition, autonomic motor neurons can continue to function even if their nerve supply is damaged, although to a lesser extent.

Where are the autonomic neurons of the nervous system located?

The ANS essentially consists of two types of neurons connected in a group. The nucleus of the first neuron is located in the central nervous system (SNS neurons begin in the thoracic and lumbar regions of the spinal cord, PNS neurons begin in the cranial nerves and sacral spinal cord). The axons of the first neuron are located in the autonomic ganglia. From the point of view of the second neuron, its nucleus is located in the autonomic ganglion, while the axons of the neurons of the second are located in the target tissue. The two types of giant neurons communicate using acetylcholine. However, the second neuron communicates with the target tissue using acetylcholine (PNS) or norepinephrine (SNS). So the PNS and SNS are connected to the hypothalamus.

Overview of the Autonomic Nervous System

Heart (control of heart rate through contraction, refractory state, cardiac conduction)
Blood vessels (constriction and dilation of arteries/veins)
Lungs (smooth muscle relaxation of bronchioles)
digestive system (gastrointestinal motility, saliva production, sphincter control, insulin production in the pancreas, and so on)
Immune system (mast cell inhibition)
Fluid balance (renal artery constriction, renin secretion)
Pupil diameter (constriction and dilation of the pupil and ciliary muscle)
sweating (stimulates the secretion of sweat glands)
Reproductive system (in men, erection and ejaculation; in women, contraction and relaxation of the uterus)
From the urinary system (relaxation and contraction of the bladder and detrusor, urethral sphincter)

The ANS, through its two branches (sympathetic and parasympathetic), controls energy expenditure. The sympathetic mediates these costs, while the parasympathetic serves the general strengthening function. All in all:

The sympathetic nervous system causes acceleration of body functions (i.e. heart rate and breathing), protects the heart, shunts blood from the extremities to the center

The parasympathetic nervous system causes the body to slow down functions (i.e. heart rate and breathing), promote healing, rest and recovery, and coordinate immune responses

Health can be negatively impacted when the influence of one of these systems is not established with the other, resulting in disruption of homeostasis. The ANS affects changes in the body that are temporary, in other words, the body must return to its baseline state. Naturally, there should not be a rapid excursion from the homeostatic baseline, but the return to the original level should occur in a timely manner. When one system is persistently activated (increased tone), health can suffer.
The departments of an autonomous system are designed to oppose (and thus balance) each other. For example, when the sympathetic nervous system begins to work, the parasympathetic nervous system begins to act to return the sympathetic nervous system back to its original level. Thus, it is not difficult to understand that the constant action of one department can cause a constant decrease in tone in another, which can lead to deterioration of health. A balance between the two is essential for health.
The parasympathetic nervous system has a faster ability to respond to changes than the sympathetic nervous system. Why have we developed this path? Imagine if we had not developed it: exposure to stress causes tachycardia, if the parasympathetic system does not immediately begin to resist, then the increased heart rate, heart rate can continue to increase to a dangerous rhythm, such as ventricular fibrillation. Because the parasympathetic is able to react so quickly, a dangerous situation like the one described cannot occur. The parasympathetic nervous system is the first to indicate changes in health in the body. The parasympathetic system is the main factor influencing respiratory activity. As for the heart, parasympathetic nerve fibers synapse deep inside the cardiac muscle, while sympathetic nerve fibers synapse on the surface of the heart. Thus, the parasympathetics are more sensitive to cardiac damage.

Transmission of vegetative impulses

Propagation along the axon, potential propagation along the axon is electrical and occurs by the exchange of + ions across the axon membrane of sodium (Na+) and potassium (K+) channels. Individual neurons generate the same potential upon receiving each stimulus and conduct the potential at a fixed rate along the axon. Velocity depends on the diameter of the axon and how heavily myelinated it is—velocity is faster in myelinated fibers because the axon is exposed at regular intervals (nodes of Ranvier). The impulse “jumps” from one node to another, skipping the myelinated sections.
Transmission is a chemical transmission resulting from the release of specific neurotransmitters from a terminal (nerve ending). These neurotransmitters diffuse across the synaptic cleft and bind to specific receptors that are attached to the effector cell or adjacent neuron. The response can be excitatory or inhibitory depending on the receptor. The transmitter-receptor interaction must occur and be completed quickly. This allows the receptors to be activated repeatedly and quickly. Neurotransmitters can be “reused” in one of three ways.

Reuptake – neurotransmitters are quickly pumped back into presynaptic nerve endings
Destruction – neurotransmitters are destroyed by enzymes located near the receptors
Diffusion – neurotransmitters can diffuse into the surrounding area and eventually be removed

Receptors – Receptors are protein complexes that cover the cell membrane. Most interact primarily with postsynaptic receptors, and some are located on presynaptic neurons, allowing more precise control of neurotransmitter release. There are two main neurotransmitters in the autonomic nervous system:

Acetylcholine is the main neurotransmitter of autonomic presynaptic fibers and postsynaptic parasympathetic fibers.
Norepinephrine is a transmitter of most postsynaptic sympathetic fibers

The answer is “rest and digest.”:

Increases blood flow to the gastrointestinal tract, which helps meet many of the metabolic needs placed on the organs of the gastrointestinal tract.
Constricts bronchioles when oxygen levels are normalized.
Controls the heart, parts of the heart through the vagus nerve and accessory nerves of the thoracic spinal cord.
Constricts the pupil, allowing you to control near vision.
Stimulates salivary gland production and accelerates peristalsis to aid digestion.
Relaxation/contraction of the uterus and erection/ejaculation in men

To understand the functioning of the parasympathetic nervous system, it would be helpful to use a real-life example:
The male sexual response is under direct control of the central nervous system. Erection is controlled by the parasympathetic system through excitatory pathways. Excitatory signals originate in the brain, through thoughts, gaze, or direct stimulation. Regardless of the origin of the nerve signal, the nerves of the penis respond by releasing acetylcholine and nitric oxide, which in turn sends a signal to the smooth muscle of the penile arteries to relax and fill with blood. This series of events leads to an erection.

Sympathetic system

Fight or Flight Answer:

Stimulates sweat glands.
Constricts peripheral blood vessels, shunting blood to the heart where it is needed.
Increases blood supply to skeletal muscles, which may be required for work.
Dilation of bronchioles under conditions of low oxygen content in the blood.
Reduced blood flow to the abdominal area, decreased peristalsis and digestive activity.
release of glucose stores from the liver increasing blood glucose levels.

As in the section on the parasympathetic system, it is useful to look at a real-life example to understand how the sympathetic nervous system functions:
An extremely high temperature is a stress that many of us have experienced. When we are exposed to high temperatures, our bodies react in the following way: heat receptors transmit impulses to the sympathetic control centers located in the brain. Inhibitory messages are sent along the sympathetic nerves to the blood vessels of the skin, which dilate in response. This dilation of blood vessels increases blood flow to the body's surface so that heat can be lost through radiation from the body's surface. In addition to dilation of the skin's blood vessels, the body also responds to high temperatures by sweating. This occurs due to an increase in body temperature, which is sensed by the hypothalamus, which sends a signal through the sympathetic nerves to the sweat glands to increase the production of sweat. Heat is lost by evaporation of the resulting sweat.

Autonomic neurons

Visceral efferent neurons are motor neurons, their job is to conduct impulses to the heart muscle, smooth muscles and glands. They can originate in the brain or spinal cord (CNS). Both visceral efferent neurons require conduction of impulses from the brain or spinal cord to the target tissue.

Preganglionic (presynaptic) neurons - the cell body of the neuron is located in the gray matter of the spinal cord or brain. It ends in the sympathetic or parasympathetic ganglion.

Preganglionic autonomic fibers - may originate in the hindbrain, midbrain, thoracic spinal cord, or at the level of the fourth sacral segment of the spinal cord. Autonomic ganglia can be found in the head, neck, or abdomen. Circuits of autonomic ganglia also run parallel on each side of the spinal cord.

The postganglionic (postsynaptic) cell body of the neuron is located in the autonomic ganglion (sympathetic or parasympathetic). The neuron ends in the visceral structure (target tissue).

Where the preganglionic fibers arise and the autonomic ganglia meet helps in differentiating between the sympathetic nervous system and the parasympathetic nervous system.

Divisions of the autonomic nervous system

Consists of internal organs (motor) efferent fibers.

Divided into sympathetic and parasympathetic divisions.

Sympathetic neurons of the CNS exit through the spinal nerves located in the lumbar/thoracic spinal cord.

Parasympathetic neurons exit the central nervous system through the cranial nerves, as well as the spinal nerves located in the sacral part of the spinal cord.

There are always two neurons involved in the transmission of nerve impulses: presynaptic (preganglionic) and postsynaptic (postganglionic).

Sympathetic preganglionic neurons are relatively short; postganglionic sympathetic neurons are relatively long.

Parasympathetic preganglionic neurons are relatively long, postganglionic parasympathetic neurons are relatively short.

All neurons of the ANS are either adrenergic or cholinergic.

Cholinergic neurons use acetylcholine (ACh) as their neurotransmitter (including: preganglionic neurons of the SNS and PNS, all postganglionic neurons of the PNS, and postganglionic neurons of the SNS that act on the sweat glands).

Adrenergic neurons use norepinephrine (NA), as do their neurotransmitters (including all postganglionic SNS neurons except those acting on the sweat glands).

Adrenal glands

Parasympathetic (craniosacral) department

Parasympathetic cranial output:
Consists of myelinated preganglionic axons that arise from the brainstem in the cranial nerves (Lll, Vll, lX and X).
Has five components.
The largest is the vagus nerve (X), conducts preganglionic fibers, contains about 80% of the total outflow.
Axons end at the end of ganglia in the walls of target (effector) organs, where they synapse with ganglion neurons.

Parasympathetic Sacral Release:
Consists of myelinated preganglionic axons that arise in the anterior roots of the 2nd through 4th sacral nerves.
Collectively they form the pelvic splanchnic nerves, with ganglion neurons synapsing in the walls of the reproductive/excretory organs.

Functions of the autonomic nervous system

Neurotransmitters of the autonomic nervous system

Some sympathetic fibers that innervate sweat glands and blood vessels within skeletal muscles secrete acetylcholine.
Adrenal medulla cells are closely associated with postganglionic sympathetic neurons; they secrete epinephrine and norepinephrine, as do postganglionic sympathetic neurons.

Receptors of the autonomic nervous system

Agonists and Antagonists

Sympathetic agonist (sympathomimetic) – a drug that stimulates the sympathetic nervous system
Sympathetic antagonist (sympatholytic) – a drug that inhibits the sympathetic nervous system
Parasympathetic agonist (parasympathomimetic) – a drug that stimulates the parasympathetic nervous system
Parasympathetic antagonist (parasympatholytic) – a drug that inhibits the parasympathetic nervous system

(One way to keep the terms straight is to think of the suffix - mimetic means "to imitate", in other words, it imitates an action. Lytic usually means "to destroy", so you can think of the suffix - lytic as inhibiting or destroying the action of the system in question) .

Response to adrenergic stimulation

Response to cholinergic stimulation

Additional actions of both sections

Combined influence of both departments

reproductive system sympathetic fiber stimulates sperm ejaculation and reflex peristalsis in women; parasympathetic fibers cause dilation of blood vessels, ultimately leading to erection of the penis in men and the clitoris in women
urinary system sympathetic fiber stimulates the urinary urge reflex by increasing the tone of the bladder; parasympathetic nerves promote bladder contraction

Organs that do not have double innervation

Adrenal medulla
sweat glands
(arrector Pili) muscle that lifts the hair
most blood vessels

These organs/tissues are innervated only by sympathetic fibers. How does the body regulate their actions? The body achieves control through an increase or decrease in the tone of sympathetic fibers (rate of excitation). By controlling the stimulation of sympathetic fibers, the action of these organs can be regulated.

Stress and ANS

Obvious disturbances related to autonomic participation

Orthostatic hypotension- Symptoms include dizziness/lightheadedness with changes in position (i.e. going from sitting to standing), fainting, blurred vision, and sometimes nausea. It is sometimes caused by a failure of the baroreceptors to sense and respond to low blood pressure caused by blood pooling in the legs.

Horner's syndrome– Symptoms include decreased sweating, drooping eyelids and pupil constriction, affecting one side of the face. This is because the sympathetic nerves that run to the eyes and face are damaged.

Disease– Hirschsprung is called congenital megacolon, this disorder has an enlarged colon and severe constipation. This is due to the absence of parasympathetic ganglia in the wall of the colon.

Vasovagal syncope– A common cause of fainting, vasovagal syncope occurs when the ANS abnormally responds to a trigger (anxious glances, straining during bowel movements, standing for long periods of time) by slowing the heart rate and dilating blood vessels in the legs, allowing blood to pool in the lower extremities, which leads to a rapid drop in blood pressure.

Raynaud's phenomenon- This disorder often affects young women, resulting in discoloration of the fingers and toes, and sometimes the ears and other areas of the body. This is caused by extreme vasoconstriction of peripheral blood vessels as a result of hyperactivation of the sympathetic nervous system. This often occurs due to stress and cold.

Spinal shock- Caused by severe trauma or injury to the spinal cord, spinal shock can cause autonomic dysreflexia, characterized by sweating, severe hypertension, and loss of bowel or bladder control as a result of sympathetic stimulation below the level of the spinal cord injury, which is not detected by the parasympathetic nervous system.

Autonomic Neuropathy

Symptoms can be variable and can affect almost all body systems:

Skin system - pale skin, lack of ability to sweat, affects one side of the face, itching, hyperalgesia (hypersensitivity of the skin), dry skin, cold feet, brittle nails, worsening symptoms at night, lack of hair growth on the lower legs

Cardiovascular system - fluttering (interruptions or missed beats), tremor, blurred vision, dizziness, shortness of breath, chest pain, ringing in the ears, discomfort in the lower extremities, fainting.

Gastrointestinal tract – diarrhea or constipation, feeling of fullness after eating small amounts (early satiety), difficulty swallowing, urinary incontinence, decreased salivation, gastric paresis, fainting while going to the toilet, increased gastric motility, vomiting (associated with gastroparesis) .

Genitourinary system - erectile dysfunction, inability to ejaculate, inability to achieve orgasm (in women and men), retrograde ejaculation, frequent urination, urinary retention (bladder fullness), urinary incontinence (stress or urinary incontinence), nocturia, enuresis, incomplete emptying of the bladder bubble

Respiratory system – decreased response to cholinergic stimulus (bronchoconstriction), impaired response to low blood oxygen levels (heart rate and efficiency of gas exchange)

Nervous system – burning in the legs, inability to regulate body temperature

Visual system – blurred/aging vision, photophobia, tubular vision, decreased tearing, difficulty focusing, loss of papillae over time

Causes of autonomic neuropathy may be associated with numerous diseases/conditions following the use of medications used to treat other diseases or procedures (eg, surgery):

Alcoholism – chronic exposure to ethanol (alcohol) can lead to disruption of axonal transport and damage to cytoskeletal properties. Alcohol has been shown to be toxic to peripheral and autonomic nerves.

Amyloidosis - in this condition, insoluble proteins settle in various tissues and organs; autonomic dysfunction is common in early hereditary amyloidosis.

Autoimmune diseases—acute intermittent and intermittent porphyria, Holmes-Adie syndrome, Ross syndrome, multiple myeloma, and POTS (postural orthostatic tachycardia syndrome) are all examples of diseases that have a suspected autoimmune component. The immune system mistakenly identifies body tissues as foreign and attempts to destroy them, resulting in widespread nerve damage.

Diabetic – Neuropathy usually occurs in diabetes, affecting both sensory and motor nerves, diabetes being the most common cause of VN.

Multiple system atrophy is a neurological disorder causing degeneration of nerve cells, resulting in changes in autonomic function and problems with movement and balance.

Nerve damage – nerves can be damaged due to injury or surgery, resulting in autonomic dysfunction

Medications – drugs used therapeutically to treat various diseases can affect the ANS. Below are some examples:

Drugs that increase the activity of the sympathetic nervous system (sympathomimetics): amphetamines, monoamine oxidase inhibitors (antidepressants), beta-adrenergic stimulants.
Drugs that reduce the activity of the sympathetic nervous system (sympatholytics): alpha and beta blockers (i.e. metoprolol), barbiturates, anesthetics.
Drugs that increase parasympathetic activity (parasympathomimetics): anticholinesterase, cholinomimetics, reversible carbamate inhibitors.
Drugs that reduce parasympathetic activity (parasympatholytics): anticholinergics, tranquilizers, antidepressants.

Obviously, people cannot control some of their risk factors that contribute to autonomic neuropathy (ie, inherited causes of VN). Diabetes is by far the largest contributing factor to VL. and places people with the disease at high risk for VL. Diabetics can reduce their risk of developing LN by closely monitoring their blood sugar to prevent nerve damage. Smoking, regular alcohol consumption, hypertension, hypercholesterolemia (high blood cholesterol) and obesity may also increase the risk of developing it, so these factors should be controlled as much as possible to reduce the risk.

Treatment of autonomic dysfunction largely depends on the cause of VN. When treating the underlying cause is not possible, doctors will try different treatments to alleviate symptoms:

Skin system - itching (pruritis) can be treated with medication or you can moisturize the skin, dryness can be the main cause of itching; cutaneous hyperalgesia can be treated with medications such as gabapentin, a drug used to treat neuropathy and nerve pain.

Cardiovascular System – Symptoms of orthostatic hypotension can be improved by wearing compression stockings, increasing fluid intake, increasing salt in the diet and medications that regulate blood pressure (ie, fludrocortisone). Tachycardia can be controlled with beta blockers. Patients should be counseled to avoid sudden changes in condition.

Gastrointestinal System – Patients may be advised to eat small, frequent meals if they have gastroparesis. Medications can sometimes be helpful in increasing mobility (ie Reglan). Increasing fiber in the diet can help with constipation. Gut retraining is also sometimes helpful for treating bowel problems. Antidepressants are sometimes helpful for diarrhea. A low-fat, high-fiber diet can improve digestion and constipation. Diabetics should strive to normalize their blood sugar.

Genitourinary system – Bladder system training, medications for overactive bladder, intermittent catheterization (used to completely empty the bladder when incomplete bladder emptying is a problem) and medications to treat erectile dysfunction (ie, Viagra) may be used for the treatment of sexual problems.

Vision issues – Medications are sometimes prescribed to help reduce vision loss.

The autonomic (autonomic, visceral) nervous system is an integral part of the human nervous system. Its main function is to ensure the functioning of internal organs. It consists of two departments, sympathetic and parasympathetic, which provide opposite effects on human organs. The work of the autonomic nervous system is very complex and relatively autonomous, almost not subject to human will. Let's take a closer look at the structure and functions of the sympathetic and parasympathetic divisions of the autonomic nervous system.

Concept of the autonomic nervous system

The autonomic nervous system consists of nerve cells and their processes. Like the normal human nervous system, the autonomic nervous system has two divisions:

• central;
• peripheral.

The central part exercises control over the functions of internal organs; this is the management department. There is no clear division into parts that are opposite in their sphere of influence. He is always involved in work, around the clock.

The peripheral part of the autonomic nervous system is represented by the sympathetic and parasympathetic divisions. The structures of the latter are found in almost every internal organ. Departments work simultaneously, but, depending on what is currently required from the body, one of them turns out to be predominant. It is the multidirectional influences of the sympathetic and parasympathetic departments that allow the human body to adapt to constantly changing environmental conditions.

Functions of the autonomic nervous system:

• maintaining a constant internal environment (homeostasis);
• ensuring all physical and mental activity of the body.

Do you have any physical activity coming up? With the help of the autonomic nervous system, blood pressure and cardiac activity will ensure sufficient minute volume of blood circulation. Are you on vacation and have frequent heart contractions? The visceral (autonomic) nervous system will cause the heart to beat more slowly.

What is the autonomic nervous system and where is “it” located?

Central department

This part of the autonomic nervous system represents various structures of the brain. It turns out that it is scattered throughout the entire brain. In the central section, segmental and suprasegmental structures are distinguished. All formations belonging to the suprasegmental department are united under the name hypothalamic-limbic-reticular complex.

Hypothalamus

The hypothalamus is a structure of the brain located in the lower part, at the base. This cannot be said to be an area with clear anatomical boundaries. The hypothalamus smoothly passes into the brain tissue of other parts of the brain.

In general, the hypothalamus consists of a cluster of groups of nerve cells, nuclei. A total of 32 pairs of nuclei were studied. Nerve impulses are formed in the hypothalamus, which reach other brain structures through various pathways. These impulses control blood circulation, breathing, and digestion. The hypothalamus contains centers for regulating water-salt metabolism, body temperature, sweating, hunger and satiety, emotions, and sexual desire.

In addition to nerve impulses, substances with a hormone-like structure are formed in the hypothalamus: releasing factors. With the help of these substances, the activity of the mammary glands (lactation), adrenal glands, gonads, uterus, thyroid gland, growth, fat breakdown, and the degree of skin color (pigmentation) is regulated. All this is possible thanks to the close connection of the hypothalamus with the pituitary gland, the main endocrine organ of the human body.

Thus, the hypothalamus is functionally connected with all parts of the nervous and endocrine systems.

Conventionally, two zones are distinguished in the hypothalamus: trophotropic and ergotropic. The activity of the trophotropic zone is aimed at maintaining the constancy of the internal environment. It is associated with a period of rest, supports the processes of synthesis and utilization of metabolic products. It exerts its main influences through the parasympathetic division of the autonomic nervous system. Stimulation of this area of ​​the hypothalamus is accompanied by increased sweating, salivation, slowing of heart rate, decreased blood pressure, vasodilation, and increased intestinal motility. The trophotropic zone is located in the anterior parts of the hypothalamus. The ergotropic zone is responsible for the body’s adaptability to changing conditions, ensures adaptation and is realized through the sympathetic division of the autonomic nervous system. At the same time, blood pressure increases, heartbeat and breathing accelerate, pupils dilate, blood sugar increases, intestinal motility decreases, and urination and bowel movements are inhibited. The ergotropic zone occupies the posterior parts of the hypothalamus.

Limbic system

This structure includes part of the temporal lobe cortex, hippocampus, amygdala, olfactory bulb, olfactory tract, olfactory tubercle, reticular formation, cingulate gyrus, fornix, and papillary bodies. The limbic system is involved in the formation of emotions, memory, thinking, ensures eating and sexual behavior, and regulates the sleep-wake cycle.

To realize all these influences, the participation of many nerve cells is necessary. The functioning system is very complex. In order for a certain model of human behavior to be formed, it is necessary to integrate many sensations from the periphery, transmitting excitation simultaneously to various structures of the brain, as if circulating nerve impulses. For example, in order for a child to remember the names of the seasons, repeated activation of structures such as the hippocampus, fornix, and papillary bodies is necessary.

Reticular formation

This part of the autonomic nervous system is called the reticular system because, like a network, it interweaves all the structures of the brain. This diffuse location allows it to participate in the regulation of all processes in the body. The reticular formation keeps the cerebral cortex in good shape, in constant readiness. This ensures instant activation of the desired areas of the cerebral cortex. This is especially important for the processes of perception, memory, attention and learning.

Individual structures of the reticular formation are responsible for specific functions in the body. For example, there is a respiratory center, which is located in the medulla oblongata. If it is affected for any reason, then independent breathing becomes impossible. By analogy, there are centers of cardiac activity, swallowing, vomiting, coughing, and so on. The functioning of the reticular formation is also based on the presence of numerous connections between nerve cells.

In general, all structures of the central part of the autonomic nervous system are interconnected through multineuron connections. Only their coordinated activity allows the vital functions of the autonomic nervous system to be realized.

Segmental structures

This part of the central part of the visceral nervous system has a clear division into sympathetic and parasympathetic structures. Sympathetic structures are located in the thoracolumbar region, and parasympathetic structures are located in the brain and sacral spinal cord.

Sympathetic department

Sympathetic centers are localized in the lateral horns in the following segments of the spinal cord: C8, all thoracic (12), L1, L2. Neurons in this area are involved in the innervation of smooth muscles of internal organs, internal muscles of the eye (regulation of pupil size), glands (lacrimal, salivary, sweat, bronchial, digestive), blood and lymphatic vessels.

Parasympathetic Division

Contains the following structures in the brain:

• accessory nucleus of the oculomotor nerve (nucleus of Yakubovich and Perlia): control of pupil size;
• lacrimal nucleus: accordingly, regulates tear secretion;
• superior and inferior salivary nuclei: provide saliva production;
• dorsal nucleus of the vagus nerve: provides parasympathetic influences on internal organs (bronchi, heart, stomach, intestines, liver, pancreas).

The sacral section is represented by neurons of the lateral horns of segments S2-S4: they regulate urination and defecation, blood flow to the vessels of the genital organs.

Peripheral department

This section is represented by nerve cells and fibers located outside the spinal cord and brain. This part of the visceral nervous system accompanies the vessels, weaving around their wall, and is part of the peripheral nerves and plexuses (related to the normal nervous system). The peripheral department also has a clear division into the sympathetic and parasympathetic parts. The peripheral department ensures the transfer of information from the central structures of the visceral nervous system to the innervated organs, that is, it carries out the implementation of what is “planned” in the central autonomic nervous system.

Sympathetic department

Represented by the sympathetic trunk, located on both sides of the spine. The sympathetic trunk is two rows (right and left) of nerve ganglia. The nodes are connected to each other in the form of bridges, moving between parts of one side and the other. That is, the trunk looks like a chain of nerve lumps. At the end of the spine, two sympathetic trunks unite into one unpaired coccygeal ganglion. In total, there are 4 sections of the sympathetic trunk: cervical (3 nodes), thoracic (9-12 nodes), lumbar (2-7 nodes), sacral (4 nodes and plus one coccygeal).

The cell bodies of neurons are located in the area of ​​the sympathetic trunk. Fibers from the nerve cells of the lateral horns of the sympathetic part of the central part of the autonomic nervous system approach these neurons. The impulse can switch on the neurons of the sympathetic trunk, or it can transit and switch on intermediate nodes of nerve cells located either along the spine or along the aorta. Subsequently, the fibers of the nerve cells, after switching, form weaves in the nodes. In the neck area it is the plexus around the carotid arteries, in the chest cavity it is the cardiac and pulmonary plexuses, in the abdominal cavity it is the solar (celiac), superior mesenteric, inferior mesenteric, abdominal aortic, superior and inferior hypogastric. These large plexuses are divided into smaller ones, from which autonomic fibers move to the innervated organs.

Parasympathetic Division

Represented by nerve ganglia and fibers. The peculiarity of the structure of this department is that the nerve nodes in which the impulse switches occur are located directly next to the organ or even in its structures. That is, the fibers coming from the “last” neurons of the parasympathetic department to the innervated structures are very short.

From the central parasympathetic centers located in the brain, impulses go as part of the cranial nerves (oculomotor, facial and trigeminal, glossopharyngeal and vagus, respectively). Since the vagus nerve is involved in the innervation of internal organs, its fibers reach the pharynx, larynx, esophagus, stomach, trachea, bronchi, heart, liver, pancreas, and intestines. It turns out that most internal organs receive parasympathetic impulses from the branching system of just one nerve: the vagus.

From the sacral sections of the parasympathetic part of the central visceral nervous system, nerve fibers go as part of the pelvic splanchnic nerves and reach the pelvic organs (bladder, urethra, rectum, seminal vesicles, prostate gland, uterus, vagina, part of the intestine). In the walls of organs, the impulse is switched in the nerve ganglia, and short nerve branches are in direct contact with the innervated area.

Metasympathetic division

It stands out as a separate separately existing department of the autonomic nervous system. It is detected mainly in the walls of internal organs that have the ability to contract (heart, intestines, ureter and others). It consists of micronodes and fibers that form a nerve plexus in the thickness of the organ. The structures of the metasympathetic autonomic nervous system can respond to both sympathetic and parasympathetic influences. But, in addition, their ability to work autonomously has been proven. It is believed that the peristaltic wave in the intestine is the result of the functioning of the metasympathetic autonomic nervous system, and the sympathetic and parasympathetic divisions only regulate the force of peristalsis.

How do the sympathetic and parasympathetic divisions work?

The functioning of the autonomic nervous system is based on the reflex arc. A reflex arc is a chain of neurons in which a nerve impulse moves in a certain direction. This can be represented schematically as follows. At the periphery, the nerve ending (receptor) picks up any irritation from the external environment (for example, cold), and transmits information about the irritation to the central nervous system (including the autonomic one) along the nerve fiber. After analyzing the received information, the autonomic system makes a decision on the response actions required by this irritation (you need to warm up so that it is not cold). From the suprasegmental parts of the visceral nervous system, the “decision” (impulse) is transmitted to the segmental parts in the brain and spinal cord. From the neurons of the central sections of the sympathetic or parasympathetic part, the impulse moves to peripheral structures - the sympathetic trunk or nerve nodes located near organs. And from these formations, the impulse along the nerve fibers reaches the immediate organ - the implementer (in the case of a feeling of cold, a contraction of smooth muscles in the skin occurs - “goosebumps”, “goose bumps”, the body tries to warm up). The entire autonomic nervous system functions according to this principle.

Law of Opposites

Ensuring the existence of the human body requires the ability to adapt. Different situations may require opposite actions. For example, when it’s hot you need to cool down (sweating increases), and when it’s cold you need to warm up (sweating is blocked). The sympathetic and parasympathetic sections of the autonomic nervous system have opposite effects on organs and tissues; the ability to “turn on” or “turn off” one or another influence allows a person to survive. What effects does activation of the sympathetic and parasympathetic divisions of the autonomic nervous system cause? Let's find out.

Sympathetic innervation provides:

Parasympathetic innervation acts as follows:

• constriction of the pupil, narrowing of the palpebral fissure, “retraction” of the eyeball;
• increased salivation, there is a lot of saliva and it is liquid;
• reduction in heart rate;
• decreased blood pressure;
• narrowing of the bronchi, increased mucus in the bronchi;
• decreased breathing rate;
• increased peristalsis up to intestinal spasms;
• increased secretion of the digestive glands;
• causes erection of the penis and clitoris.

There are exceptions to the general pattern. There are structures in the human body that have only sympathetic innervation. These are the walls of blood vessels, sweat glands and the adrenal medulla. Parasympathetic influences do not apply to them.

Typically, in the body of a healthy person, the influences of both departments are in a state of optimal balance. There may be a slight predominance of one of them, which is also a variant of the norm. The functional predominance of excitability of the sympathetic department is called sympathicotonia, and the parasympathetic department is called vagotonia. Some periods of human age are accompanied by an increase or decrease in the activity of both departments (for example, activity increases during adolescence, and decreases during old age). If there is a predominant role of the sympathetic department, then this is manifested by sparkle in the eyes, wide pupils, a tendency to high blood pressure, constipation, excessive anxiety and initiative. The vagotonic effect is manifested by narrow pupils, a tendency to low blood pressure and fainting, indecision, and excess body weight.

Thus, from the above it becomes clear that the autonomic nervous system with its oppositely directed sections ensures human life. Moreover, all structures work in harmony and coordination. The activity of the sympathetic and parasympathetic departments is not controlled by human thinking. This is exactly the case when nature turned out to be smarter than man. We have the opportunity to engage in professional activities, think, create, leave ourselves time for small weaknesses, being confident that our own body will not let us down. Internal organs will work even when we are resting. And this is all thanks to the autonomic nervous system.

Educational film “The Autonomic Nervous System”

Activation of the parasympathetic nervous system. The parasympathetic nervous system regulates processes associated with energy production (food intake, digestion, absorption) and its accumulation. These processes occur in the body at rest with minimal tidal volume (the bronchi are narrowed) and heart activity.

Secretions from the glands and intestines ensure digestion. Food moves through the intestines due to increased peristalsis and decreased sphincter tone. The smooth muscles of the bladder walls contract, the sphincters relax, which facilitates urination. Excitation of the parasympatheticus (see below) leads to a narrowing of the pupil and an increase in the curvature of the lens, improving close vision (accommodation).

The structure of the parasympathetic nerve. The bodies of preganglionic parasympathetic fibers are located in the brain stem and in the sacral segment of the spinal cord. Fibers emerge from the brainstem as part of

The seventh pair (N. facialis) and G. pterygopalatinum or G. submandibulare to the lacrimal, as well as submandibular and sublingual salivary glands

Ninth pair (N. glossopharyngeus) and G. oticum to Glandula parotis

Tenth pair (N. vagus) to the organs of the chest and abdominal cavity.

About 75% of all parasympathetic nerve fibers are contained in N. vagus. The neurons of the sacral parasympathetic nerve innervate the large intestine, rectum, bladder, lower urethra, and external genitalia.

Acetyl choline. Acetylcholine (ACh) is a neurotransmitter at postganglionic parasympathetic synapses, as well as ganglion synapses (sympathetic and parasympathetic nerves) and the motor end plate (p. 190). However, at these synapses acetylcholine acts on different types of receptors (see table below).

The presence of various receptors in cholinergic synapses makes it possible to act on them specifically with the help of pharmacological agents.

© R.R. Wenzel, Yu.V. Furmenkova, 2002
UDC 611.839-08
Received November 8, 2001

R.R. Wenzel, Yu.V. Furmenkova

State Medical Academy, Nizhny Novgorod;
University Hospital, Essen (Germany)

Antihypertensive drugs and the sympathetic nervous system

The sympathetic nervous system (SNS) is an important regulator of cardiovascular activity. Its activity is determined by psychological, nervous and humoral factors. Activation of neurohumoral systems, as well as disruption of local regulatory mechanisms, plays an important role in the development and prognosis of cardiovascular diseases.

SNS activity increases with age, regardless of the presence of pathological conditions 2 . In congestive heart failure, significant increases in sympathetic activity correlate with mortality rates 3 . Hypersympathicotonia contributes to the development of myocardial ischemia due to reflex tachycardia and narrowing of the coronary vessels, combined with the presence of arterial hypertension (AH), insulin resistance and a high risk of developing cardiovascular complications 4, 5. Although the contribution of the SNS to the development of hypertension is controversial, the role of hypersympathicotonia in the early stages of the disease is beyond doubt 6-8. It is believed that essential hypertension is associated with increased sympathetic activity at the level of the central nervous system 2, 7, 9. However, it is possible that as a result of the interaction of neuronal plexuses and pathways involved in the regulation of sympathetic activity at the central level, blood pressure (BP) and the risk of vascular complications may be reduced. Pharmacotherapy of hypertension and its effect on the activity of the SNS served as the topic of this article.

Regulation of the sympathetic nervous system

Efferent fibers of the medulla oblongata connect it to the vasomotor center. Innervation of internal organs is carried out by two neurons united in a ganglion. Myelinated axons of preganglionic neurons of the thoracic and lumbar spinal cord approach postganglionic neurons of the sympathetic trunk and prevertebral ganglia. The mediator of nerve impulse transmission from the presynaptic to the postsynaptic neuron is acetylcholine, which binds to nicotine-sensitive receptors. The mediator of adrenergic receptors, norepinephrine, participates in the transmission of impulses to effector organs.

The catecholamines epinephrine, norepinephrine and dopamine are produced in the adrenal glands, which are phylogenetically a ganglion. In peripheral vessels, sympathetic activation causes vasoconstriction, mediated by the action of beta-adrenergic receptors on smooth muscle cells and beta-adrenergic receptors on the heart. Experimental and early clinical data have shown that a2-adrenergic receptors have a secondary role in the sympathetic regulation of the cardiovascular system, but endothelial a2-adrenergic receptors are directly involved in adrenergic vasoconstriction 10, 11.

The SNS interacts with the renin-angiotensin system (RAS) and the vascular endothelium. Angiotensin (AT) II influences the release and reuptake of norepinephrine by presynaptic receptors 12 and activates the SNS through central mechanisms 13 , 14 . Moreover, stimulation of b1-adrenergic receptors of the juxtaglomerular apparatus leads to activation of the RAS due to an increase in renin concentration 15 ; this mechanism, as well as sodium and water retention, contributes to an increase in blood pressure.

In addition to histamine, dopamine and prostaglandins, the production of norepinephrine in presynaptic receptors is inhibited by norepinephrine itself through a feedback regulation mechanism, while the presynaptic release of norepinephrine is stimulated by epinephrine and AT II.

Methods for studying the activity of the sympathetic nervous system

There are various ways to study the activity of the SNS. Well-known indirect methods include measurements of blood pressure, blood flow velocity and heart rate (HR). However, the interpretation of these data is difficult, since the reaction of effector organs to changes in sympathetic activity is slow and also depends on local chemical, mechanical and hormonal influences. In clinical practice, SNS activity is determined by the concentration of norepinephrine in the blood plasma. But the level of norepinephrine as an adrenergic neurotransmitter released from synaptic endings is also an indirect indicator. In addition, plasma concentrations of norepinephrine reflect the activity of not only adrenergic neurons, but also the adrenal glands. Methods for measuring plasma catecholamines have varying degrees of accuracy 16 , so other methods such as heart rate variability and blood pressure studies are worth considering 17 , 18 .

Microneurography allows direct determination of cutaneous or muscular sympathetic activity in the peripheral nerve 19 , 20 . Nerve impulses are recorded at the moment of their occurrence, and it is possible not only to observe their changes in response to stimulation, but also to monitor them 19-23. This is a direct method of measuring SNS activity in the medulla oblongata. New advances in microneurography make it possible to characterize changes in the activity of sympathetic nerves in response to cardiovascular drugs and analyze the pharmacokinetic capabilities of the latter 24 .

In addition, information about the influence of the SNS on effector organs is provided by measuring systolic intervals, cardiac impedanceography, plethysmography and laser Dopplerography 16, 25-28.

Effect of drugs on the sympathetic nervous system

Beta blockers

β-Adrenergic receptor antagonists reduce the positive inotropic and chronotropic effects of catecholamines mediated through β1-adrenergic receptors and β2-adrenergic relaxation of vascular smooth muscle cells 29-32. In addition, blockade of b-adrenergic receptors inhibits the metabolic effects of catecholamines such as lipolysis or glycogenolysis 31.

In the treatment of cardiovascular diseases, selective blockade of b1 receptors protects the heart from excessive sympathetic stimulation, reducing the frequency and force of heart contractions, and as a result, myocardial oxygen consumption 31.

Beta-blockers are the drugs of choice in the treatment of hypertension and coronary heart disease (CHD) because they reduce mortality, the incidence of ischemic episodes, the risk of primary and recurrent myocardial infarction, and sudden coronary death 33-36.

In recent years, β-adrenergic antagonists have been used in the treatment of congestive heart failure 37–39. The positive effect of b-adrenergic receptor blockade in heart failure, leading, apparently, to better functioning of the SNS, is observed with bisoprolol 40, metoprolol 41 and carvedilol 42. It has been proven that these drugs not only improve hemodynamics and clinical symptoms, but also reduce mortality 42, 43, although at the beginning of treatment, during the selection of an adequate dose in cases of severe heart failure, mortality may increase. Thus, β-adrenergic receptor antagonists improve the sensitivity of the latter to their agonists 44. On the central link of the sympathetic nervous system, b-blockade has the opposite effect, which has not been studied enough 45, 46. Although sympathetic nerve activity increased with intravenous administration of the β1-selective β-blocker metoprolol to patients with untreated hypertension 45 , it decreased with long-term use of this drug 46 . Interestingly, the effect of selective b1- and non-selective b-blockers on SNS activity differs, at least after the first dose in healthy volunteers. At the same time, the level of catecholamines in plasma increases significantly after administration of the beta-selective beta-blocker bisoprolol, while administration of the non-selective beta-blocker propranolol does not affect the plasma concentration of norepinephrine 29, 31.

Diuretics

Diuretics inhibit the reabsorption of salts and water in the tubules, which reduces pre- and afterload. The increased release of salt and water ions under the influence of diuretics activates not only vasopressin, the renin-angiotensin-aldosterone system, but also the SNS, which compensates for disturbances in the water-salt balance 47.

Nitrates

Nitrates, as peripheral vasodilators, cause endothelium-dependent relaxation of vascular smooth muscle cells. Side effects of some drugs in this group include reflex tachycardia. In a double-blind, placebo-controlled study, isosorbide dinitrate markedly increased both heart rate and, as measured by microneurography, SNS activity 24 . This confirms the results of studies of the effects of other vasodilators when administered intravenously 48-50. This effect can be explained by the fact that, following a possible decrease in central venous pressure, pulse pressure decreases and baroreceptors are activated 24 .

Other vasodilators, including a1-blockers

The vasodilators minoxidil and hydrolasine effectively lower blood pressure by reducing pre- and afterload. However, they stimulate the SNS, so during long-term treatment, compensatory activation of the sympathetic and renin-angiotensin systems predominates 51 .

Selective α1-adrenergic receptor antagonists, such as prazosin, also reduce pre- and afterload by inhibiting peripheral sympathetic vasoconstriction, but do not affect the sympathetic activity of the myocardium, since it contains mainly β-adrenergic receptors 52. This explains why the Veterans Administration Cooperative Study (VACS) trial, which used prazosin, did not demonstrate an improvement in prognosis in patients with heart failure 53 . It should be noted that the α1-adrenergic receptor antagonist doxazosin significantly activates the SNS, both at rest and during exercise, compared to placebo 29, 54.

Calcium ion antagonists

Calcium antagonists (CAs) cause peripheral vasodilation and inhibition of the effect of vasoconstrictors on smooth muscle due to blockade of slow L-type calcium channels and a decrease in calcium ion transport. A decrease in the intracellular concentration of the latter inhibits electromechanical processes, which leads to vasodilation and a decrease in blood pressure. Representatives of three groups of calcium antagonists - dihydropyridine (nifedipine), phenylalkylamine (verapamil) and benzodiazipine (diltiazem) types bind different parts of the α1 subunit of the calcium channel. If drugs of the dihydropyridine group are predominantly peripheral vasodilators, then substances like verapamil may directly act on the sinoatrial node and probably reduce the activity of the SNS.

AA have positive antihypertensive and antiischemic effects 55 . Moreover, they have vasoprotective capabilities, improve endothelial function in atherosclerosis and hypertension, both experimentally and in the treatment of patients with hypertension 56, 57. AA inhibit the proliferation of smooth muscle cells in human coronary arteries 58 and, to some extent, the progression of atherosclerosis 59–67.

Despite the vasoprotective effect, clinical studies of AK in patients with coronary artery disease, impaired left ventricular function, and diabetes did not give a positive result 60-67.

Activation of the SNS depends not only on the group of AAs used, but also on their pharmacokinetics. For example, dihydropyridine AKs (i.e. nifedipine, felodipine, amlodipine) increase SNS activity and cause reflex tachycardia 68, 69. On the contrary, verapamil reduces heart rate and, as shown by plasma norepinephrine studies, SNS activity 70 . A single dose of nifedipine to healthy volunteers, according to microneurography, increased the tone of the SNS, which was typical for both short- and long-acting drugs. However, nifedipine has different effects on the sympathetic nerves leading to the heart and blood vessels. Thus, heart rhythm was not an accurate indicator of the state of the nervous system and a slight increase in heart rate did not indicate a decrease in sympathetic activity 68 .

Amlodipine, a new long-acting AA, appears to stimulate the SNS to a lesser extent than other dihydropyridine drugs. Although heart rate and plasma norepinephrine levels in hypertensive patients increased significantly during an acute drug test with amlodipine, no effect on heart rate was observed with long-term use 69 .

Angiotensin-converting enzyme inhibitors

By blocking the enzyme, angiotensin-converting enzyme (ACE) inhibitors disrupt the synthesis of AT II, ​​a powerful vasoconstrictor that increases the release of norepinephrine by stimulating peripheral presynaptic receptors 71. Moreover, AT II stimulates the activity of the central division of the SNS 72 . It is believed that ACE inhibitors also prevent inhibition of bradykinin synthesis and thereby promote vasodilation. Bradykinin promotes the release of nitric oxide and prostacyclin from the endothelium, which enhances the hemodynamic response to ACE blockade. However, bradykinin can also have side effects, in particular cough and vascular edema 73-77.

Unlike vasodilators (nitrates or calcium antagonists) that activate the SNS, ACE inhibitors do not cause reflex tachycardia and increase plasma norepinephrine levels 78 . In a double-blind, placebo-controlled study, the ACE inhibitor captopril, administered intravenously to healthy volunteers, reduced sympathetic nerve activity despite lowering blood pressure and did not alter the response to mental or physical stress, whereas nitrates caused significant activation of the SNS 3, 24. Thus, a decrease in the plasma concentration of AT II, ​​which stimulates the activity of the SNS, reduces the tone of the SNS 72. This is the only possible explanation for the beneficial effect of ACE inhibitors on survival in patients with left ventricular dysfunction, in whom increased SNS tone was associated with high mortality 79 . The beneficial effects of ACE inhibitors on morbidity and mortality in patients with heart failure and left ventricular dysfunction, as well as in patients with myocardial infarction, have been reported in many clinical studies 79–83.

However, there are a number of mechanisms that partially offset the beneficial effects of ACE inhibitors noted with acute intravenous administration. First of all, AT II can be synthesized in an alternative way, independent of ACE, with the help of chymases; at the same time, the SNS is inhibited to a lesser extent 84-86. On the other hand, it has been established that chronic ACE inhibition does not alter the biosynthesis, accumulation and release of catecholamines 87. Since bradykinin dose-dependently stimulates the release of norepinephrine, even during blockade of the converting enzyme, it can be considered to compensate for the lack of effect of ACE inhibitors by promoting the release of catecholamines 87. In heart failure, chronic treatment with ACE inhibitors is accompanied by a marked decrease in central sympathetic activity, possibly due to the effect of constantly stressed baroreflex mechanisms on the SNS 88 . The activity of the parasympathetic nervous system does not appear to change with acute and chronic administration of ACE inhibitors, since these drugs do not affect basic cardiovascular reflexes 89 .

Angiotensin type I receptor antagonists

Blockade of AT II receptors is the most direct way to inhibit the RAS. Unlike ACE inhibitors, which do not affect the release of norepinephrine due to inhibition of its reuptake and metabolism, activation of compensatory mechanisms, angiotensin type I receptor antagonists (ATI) in vitro suppress angiotensin-induced norepinephrine uptake and, therefore, its proliferative effect 90, 91.

The effect of AT I receptor antagonists in the human body in vivo has not yet been sufficiently studied. A study of the efficacy of losartan in the elderly showed that the AT I receptor antagonist losartan had a greater effect on morbidity and mortality in patients with symptomatic heart failure than the ACE inhibitor captopril 92 . There were no differences in plasma concentrations of norepinephrine between the groups of patients receiving losartan and captopril.

Experimental data have shown that AT I receptor antagonists suppress catecholamine synthesis to a greater extent than ACE inhibitors 93 . It has been established that the new non-peptide AT I receptor antagonist eprosartan inhibits the pressor response to spinal cord stimulation in rats, while losartan, valsartan and irbesartan do not affect the SNS. This fact can be regarded as a more pronounced inhibition of AT II receptors 94 .

It is unknown whether these effects on the SNS will be significant in vivo. However, the first clinical results of a double-blind, placebo-controlled study showed that, at least, losartan did not reduce SNS activity at rest or after exercise compared with placebo or enalapril 54 .

Central sympatholytics

Clonidine, guafacin, guanabenz and a-methyl-DOPA are well-known antihypertensive drugs that act on central α2-adrenergic receptors 95 and lead to depression of the SNS and a decrease in blood pressure, mainly as a result of vasodilation and a subsequent decrease in peripheral vascular resistance. Despite their good hypotensive effect, these substances are no longer used as first-line agents in the treatment of hypertension due to their unwanted side effects such as nausea, dry mouth and drowsiness. Withdrawal syndrome is also possible with clonidine use 96 . These side effects are mainly related to the action on α2-adrenergic receptors 97 .

Clinical use of a new generation of centrally acting antihypertensive drugs (for example, moxonidine and rilmenidine) with fewer side effects has now begun. It has been established that they have a greater effect on central imidazoline1 receptors than on a2-adrenergic receptors 97-99. In contrast, other centrally acting antihypertensive drugs (α-methyl-DOPA, guanfacine, guanabenz) interact predominantly with central α2 receptors 95 . In laboratory animals, moxonidine inhibited the sympathetic innervation of resistive vessels, the heart and kidneys 97, 100. A double-blind, placebo-controlled in vivo study with direct measurement of SNS activity using microneurography demonstrated for the first time that the imidazoline-1 receptor agonist moxonidine reduces systolic and diastolic blood pressure due to a decrease in central SNS tone in both healthy volunteers and untreated hypertensive patients 68 . Moxonidine reduces sympathetic activity and plasma norepinephrine levels in both groups, while the concentrations of epinephrine and renin did not change 68. Heart rate after taking moxonidine decreased in healthy individuals; in patients with hypertension, a tendency to bradycardia was observed only at night 68.

In terms of its ability to control blood pressure, moxonidine is comparable to other antihypertensive drugs, such as a- and b-blockers, calcium antagonists or ACE inhibitors; side effects (nausea, dry mouth) are less pronounced than with clonidine and other centrally acting drugs of the previous generation 30, 101.

Rilmenidine is another imidazoline 1 receptor agonist with even greater affinity for the latter 102 . Its use in patients has shown effective blood pressure lowering with fewer side effects than clonidine 103-105. Rilmenidine caused the same reduction in blood pressure as the beta-adrenergic receptor antagonist atenolol, but was better tolerated by patients compared to it. However, unlike atenolol, it did not affect measures of autonomic nervous system function such as heart rate during exercise and the Valsalva maneuver 106 . The effect of rilmenidine on the central nervous system has not yet been studied.

Interaction between the sympathetic nervous system and the vascular endothelium

The vascular endothelium plays an important role in regulating their tone. Impaired secretion of mediators by the endothelium may be one of the links in the pathogenesis and progression of hypertension and atherosclerosis. Experimental data have shown the presence of a variety of interactions between the SNS and the vascular endothelium. Endothelin-1, produced by endothelial cells, is a powerful vasoconstrictor; its plasma concentration correlates with mortality rates from severe cardiovascular disease 107 , 108 . Endothelin causes peripheral vasoconstriction and increased blood pressure; in rats, endothelin administration stimulates sympathetic activity 109 . In addition, this substance is considered a comitogen for the proliferation of vascular smooth muscle cells 108.

Endothelin receptors are coupled to calcium channels via G proteins 110 . This fact may explain how calcium antagonists reduce endothelium-dependent vasoconstriction. A blood flow study in the forearm showed that verapamil or nifedipine administered intraarterially prevented the constrictor response to intravenous endothelin infusion 28 . On the other hand, drugs that activate the SNS (eg, nitrates and nifedipine) increase plasma endothelin concentrations in humans, whereas ACE inhibitors and moxonidine inhibit SNS activity and do not affect endothelin levels 24, 111.

Long-term therapy with calcium antagonists experimentally and in patients with hypertension improves endothelium-dependent relaxation in response to acetylcholine 112 . ACE inhibitors also stimulate endothelium-dependent relaxation by inhibiting the inactivation of bradykinin, which leads to the formation of nitric oxide and prostacyclin. When studying blood flow in resistive vessels in rats with spontaneous hypertension, it was found that long-term blockade of the RAS with the non-peptide AT II receptor antagonist CGP 48369, the ACE inhibitor benazepril or the calcium antagonist nifedipine reduced blood pressure and improved endothelial function 56 . Clinical studies have shown that the ACE inhibitor quinapril is able to reverse diastolic dysfunction and reduce the incidence of coronary ischemia 113–115. Administration of the ACE inhibitor lisinopril to patients with essential hypertension selectively enhances vasodilation in response to bradykinin 116 .

Different ACE inhibitors, such as quinapril and enalapril, improve endothelium-dependent vasodilation to varying degrees, apparently having different affinities for ACE. This is supported by the fact that quinapril, in contrast to enalapril, promotes vascular dilation in patients with chronic heart failure by increasing nitric oxide 117 .

Experimental and early clinical studies of the cutaneous microcirculation in humans suggest that adrenergic agonists stimulate endothelial α-receptors and this leads to the release of nitric oxide 10, 118. Indeed, a1 receptor-mediated constriction of vascular smooth muscle cells is enhanced by nitric oxide inhibition both in vitro and in vivo 10, 118. This mechanism may have pathophysiological significance in the development of atherosclerosis and hypertension when endothelial function is impaired. The effect of other drugs on the endothelium has not yet been clarified.

Conclusion

The effects of cardiovascular drugs on the SNS are important. However, in most cases, SNS activity has been studied using indirect methods, such as analysis of heart rate variability or plasma catecholamines. In contrast, microneurography allows direct assessment of the conduction of nerve impulses along central sympathetic fibers.

The complex effect of antihypertensive drugs on pressor systems (SNS, RAS and endothelin) is clinically important, especially in the treatment of patients with diseases of the cardiovascular system. Activation of the SNS is a possible cause of side effects of many drugs. The fact that plasma norepinephrine levels predict death in patients with heart failure 3, 119, 120 suggests that they have increased SNS activity, which is also possible in other patients, especially those with hypertension 121. In addition, SNS hyperactivity can be detected in patients with diabetes mellitus and coronary artery disease, including acute coronary syndrome 122 .

The answer to the question whether the positive effect of antihypertensive drugs on the sympathetic nervous system reduces cardiovascular and overall mortality can be obtained through invasive studies.

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In this article we will look at what the sympathetic and parasympathetic nervous systems are, how they work, and what are their differences. We have previously covered the topic as well. The autonomic nervous system, as is known, consists of nerve cells and processes, thanks to which the regulation and control of internal organs occurs. The autonomic system is divided into peripheral and central. If the central one is responsible for the work of internal organs, without any division into opposite parts, then the peripheral one is divided into sympathetic and parasympathetic.

The structures of these departments are present in every internal organ of a person and, despite their opposing functions, they work simultaneously. However, at different times, one or another department turns out to be more important. Thanks to them, we can adapt to different climatic conditions and other changes in the external environment. The autonomic system plays a very important role; it regulates mental and physical activity, and also maintains homeostasis (constancy of the internal environment). If you rest, the autonomic system engages the parasympathetic system and the number of heartbeats decreases. If you start running and experience heavy physical activity, the sympathetic department turns on, thereby speeding up the heart and blood circulation in the body.

And this is only a small slice of the activity that the visceral nervous system carries out. It also regulates hair growth, contraction and dilation of pupils, the functioning of one or another organ, is responsible for the psychological balance of the individual, and much more. All this happens without our conscious participation, which is why at first glance it seems difficult to treat.

Sympathetic nervous system

Among people who are unfamiliar with the work of the nervous system, there is an opinion that it is one and indivisible. However, in reality everything is different. Thus, the sympathetic department, which in turn belongs to the peripheral, and the peripheral belongs to the autonomic part of the nervous system, supplies the body with the necessary nutrients. Thanks to its work, oxidative processes proceed quite quickly, if necessary, the work of the heart accelerates, the body receives the proper level of oxygen, and breathing improves.

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Interestingly, the sympathetic division is also divided into peripheral and central. If the central part is an integral part of the work of the spinal cord, then the peripheral part of the sympathetic has many branches and nerve nodes that connect. The spinal center is located in the lateral horns of the lumbar and thoracic segment. The fibers, in turn, extend from the spinal cord (1st and 2nd thoracic vertebrae) and 2,3,4 lumbar vertebrae. This is a very brief description of where the sympathetic system is located. Most often, the SNS is activated when a person finds himself in a stressful situation.

Peripheral department

It is not so difficult to imagine the peripheral part. It consists of two identical trunks, which are located on both sides along the entire spine. They start from the base of the skull and end at the tailbone, where they converge into a single unit. Thanks to the internodal branches, the two trunks are connected. As a result, the peripheral section of the sympathetic system passes through the cervical, thoracic and lumbar regions, which we will consider in more detail.

• Cervical region. As you know, it starts from the base of the skull and ends at the transition to the thoracic (cervical 1st ribs). There are three sympathetic nodes here, which are divided into lower, middle and upper. All of them pass behind the human carotid artery. The upper node is located at the level of the second and third cervical vertebrae, has a length of 20 mm, a width of 4 - 6 millimeters. The middle one is much more difficult to find, as it is located at the intersections of the carotid artery and the thyroid gland. The lower node has the largest size, sometimes even merging with the second thoracic node.
• Thoracic department. It consists of up to 12 nodes and has many connecting branches. They reach out to the aorta, intercostal nerves, heart, lungs, thoracic duct, esophagus and other organs. Thanks to the thoracic region, a person can sometimes feel the organs.
• The lumbar region most often consists of three nodes, and in some cases has 4. It also has many connecting branches. The pelvic region connects the two trunks and other branches together.

Parasympathetic Division

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This part of the nervous system begins to work when a person tries to relax or is at rest. Thanks to the parasympathetic system, blood pressure decreases, blood vessels relax, pupils constrict, heart rate slows down, and sphincters relax. The center of this department is located in the spinal cord and brain. Thanks to efferent fibers, the hair muscles relax, sweat secretion is delayed, and blood vessels dilate. It is worth noting that the structure of the parasympathetic includes the intramural nervous system, which has several plexuses and is located in the digestive tract.

The parasympathetic department helps to recover from heavy loads and performs the following processes:

• Reduces blood pressure;
• Restores breathing;
• Dilates blood vessels in the brain and genital organs;
• Constricts the pupils;
• Restores optimal glucose levels;
• Activates the digestive secretion glands;
• Tones the smooth muscles of internal organs;
• Thanks to this department, cleansing occurs: vomiting, coughing, sneezing and other processes.

In order for the body to feel comfortable and adapt to different climatic conditions, the sympathetic and parasympathetic parts of the autonomic nervous system are activated at different times. In principle, they work constantly, however, as mentioned above, one of the departments always prevails over the other. Once in the heat, the body tries to cool itself and actively secretes sweat; when it urgently needs to warm up, sweating is accordingly blocked. If the autonomic system works correctly, a person does not experience certain difficulties and does not even know about their existence, except for professional necessity or curiosity.

Since the topic of the site is dedicated to vegetative-vascular dystonia, you should know that due to psychological disorders, the autonomic system experiences disruptions. For example, when a person has suffered a psychological trauma and experiences a panic attack in a closed room, his sympathetic or parasympathetic department is activated. This is a normal reaction of the body to an external threat. As a result, a person feels nausea, dizziness and other symptoms, depending on. The main thing is that the patient should understand that this is only a psychological disorder, and not physiological deviations, which are only a consequence. This is why medication treatment is not an effective remedy; they only help relieve symptoms. For a full recovery, you need the help of a psychotherapist.

If at a certain point in time the sympathetic department is activated, blood pressure increases, the pupils dilate, constipation begins, and anxiety increases. When the parasympathetic action occurs, the pupils constrict, fainting may occur, blood pressure decreases, excess weight accumulates, and indecision appears. The most difficult thing is for a patient suffering from a disorder of the autonomic nervous system when he has it, since at this moment disorders of the parasympathetic and sympathetic parts of the nervous system are simultaneously observed.

As a result, if you suffer from a disorder of the autonomic nervous system, the first thing you should do is undergo numerous tests to rule out physiological pathologies. If nothing is revealed, it is safe to say that you need the help of a psychologist who will quickly relieve you of your illness.