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Chapter: Modern Pharmacology with Clinical Applications: General Organization and Functions of the Nervous System

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Innervation of Various Organs by the Sympathetic and Parasympathetic Nervous Systems

Many visceral organs are innervated by both divisions of the autonomic nervous system.

INNERVATION OF VARIOUS ORGANS BY THE SYMPATHETIC AND PARASYMPATHETIC NERVOUS SYSTEMS

Many visceral organs are innervated by both divisions of the autonomic nervous system. In most instances, when an organ receives dual innervation, the two sys-tems work in opposition to one another. In some tissues and organs, the two innervations exert an opposing in-fluence on the same effector cells (e.g., the sinoatrial node in the heart), while in other tissues opposing ac-tions come about because different effector cells are ac-tivated (e.g., the circular and radial muscles in the iris).

Some organs are innervated by only one division of the autonomic nervous system.

Many neurons of both divisions of the autonomic nervous system are tonically active; that is, they are con-tinually carrying some impulse traffic. The moment-to-moment activity of an organ such as the heart, which re-ceives a dual innervation by sympathetic (noradrenergic) and parasympathetic (cholinergic) neurons, is controlled by the level of tonic activity of the two systems.

Blood Vessels

Most vascular smooth muscle is innervated solely by the sympathetic (noradrenergic) nervous system, but there are exceptions. Some blood vessels in the face, tongue, and urogenital tract (especially the penis) are innervated by parasympathetic (cholinergic) as well as sympathetic (noradrenergic) neurons. The parasympathetic innerva-tion of blood vessels has only regional importance, for ex-ample, in salivary glands, where increased parasympa-thetic activity causes vasodilation that supports salivation.

The primary neural control of total peripheral re-sistance is through sympathetic nerves. The diameter of blood vessels is controlled by the tonic activity of nor-adrenergic neurons. There is a continuous outflow of noradrenergic impulses to the vascular smooth muscle, and therefore some degree of constant vascular con-striction is maintained. An increase in impulse outflow causes further contraction of the smooth muscle, result-ing in greater vasoconstriction. A decrease in impulse outflow permits the smooth muscle to relax, leading to vasodilation.

The Heart

The heart is innervated by both sympathetic and parasympathetic neurons; however, their distribution in the heart is quite different. Postganglionic noradrener-gic fibers from the stellate and inferior cervical ganglia innervate the sinoatrial (S-A) node and myocardial tis-sues of the atria and ventricles. Activation of the sym-pathetic outflow to the heart results in an increase in rate (positive chronotropic effect), in force of contrac-tion (positive inotropic effect), and in conductivity of the atrioventricular (A-V) conduction tissue (positive dro-motropic effect).

The postganglionic cholinergic fibers of the para-sympathetic nervous system terminate in the S-A node, atria, and A-V conduction tissue. Cholinergic fibers do not innervate the ventricular muscle to any significant degree. Activation of the parasympathetic outflow to the heart results in a decrease in rate (negative chronotropic effect) and prolongation of A-V conduc-tion time (negative dromotropic effect). There is a de-crease in the contractile force of the atria but little ef-fect on ventricular contractile force.

The effect of a drug on the heart depends on the bal-ance of sympathetic and parasympathetic activity at the time the drug is administered. An example is the effect of the ganglionic blocking agents , which nonselectively inhibit transmission in both sym-pathetic and parasympathetic ganglia. Normally, during rest or mild activity, the heart is predominantly under the influence of the vagal parasympathetic system. Blockade of the autonomic innervation of the heart by the administration of a ganglionic blocking agent accel-erates the heart rate. Conversely, if sympathetic activity is dominant, as in exercise, ganglionic blockade will de-crease the heart rate and also reduce ventricular con-tractility. Likewise, the magnitude of effect of a drug an-tagonist of sympathetic activity will depend upon how much sympathetic activity exists at the time it is given. A similar relationship exists between parasympathetic antagonists and the level of parasympathetic activity.

Cardiovascular Reflexes

Any sudden alteration in the mean arterial blood pres-sure tends to produce compensatory reflex changes in heart rate, contractility, and vascular tone, which will oppose the initial pressure change and restore the homeostatic balance. The primary sensory mechanisms that detect changes in the mean arterial blood pressure are stretch receptors (baroreceptors) in the carotid sinus and aortic arch.

The injection of a vasoconstrictor, which causes an increase in mean arterial blood pressure, results in acti-vation of the baroreceptors and increased neural input to the cardiovascular centers in the medulla oblongata. The reflex compensation for the drug-induced hyper-tension includes an increase in parasympathetic nerve activity and a decrease in sympathetic nerve activity. This combined alteration in neural firing reduces car-diac rate and force and the tone of vascular smooth muscle. As a consequence of the altered neural control of both the heart and the blood vessels, the rise in blood pressure induced by the drug is opposed and blunted.

Injection of a drug that causes a fall in the mean ar-terial blood pressure triggers diametrically opposite re-flex changes. There is decreased impulse traffic from the cardiac inhibitory center, stimulation of the cardiac ac-celerator center, and augmented vasomotor center ac-tivity. These changes in cardiac and vasomotor center activity accelerate the heart and increase sympathetic transmission to the vasculature; thus, the drug-induced fall in blood pressure is opposed and blunted.

The Eye

Two sets of smooth muscle in the iris control the diameter of the pupil. One set of muscles, which is arranged radially (dilator pupillae), is innervated by sympathetic (norad- renergic) fibers that arise from cells in the superior cervi-cal ganglion. Stimulation of them causes contraction of the radial smooth muscle cells, leading to dilation of the pupil (mydriasis). The other set of smooth muscle cells in the iris (constrictor pupillae) is circular and is innervated by parasympathetic neurons arising from cells in the cil-iary ganglion. Stimulation of these cholinergic neurons causes contraction of the circular smooth muscle of the iris and constriction of the pupil (miosis).

The lens, which aids in visual accommodation, is at-tached at its lateral edge to the ciliary body by suspensory ligaments. When the smooth muscles of the ciliary body are relaxed, the ciliary body exerts tension on the lens, causing it to flatten.Thus, the eye is accommodated for far vision. Stimulation of parasympathetic cholinergic neu-rons, which arise in the ciliary ganglion, causes contraction of the smooth muscle of the ciliary body; this decreases the lateral tension on the lens. Naturally elastic, the lens thickens, and the eye accommodates for near vision. Drugs that block accommodation are called cycloplegic. Since the parasympathetic system is dominant in the eye, blockade of this system by atropine or of both autonomic systems by a ganglionic blocking agent will result in pupil-lary dilation and a loss of accommodative capacity.

Pulmonary Smooth Muscle

The bronchial tree is innervated by both divisions of the autonomic nervous system. Postganglionic parasympa-thetic neurons innervate bronchial smooth muscle di-rectly and produce bronchoconstriction when stimu-lated. Sympathetic noradrenergic neurons appear to innervate vascular smooth muscle and parasympathetic ganglion cells. The effect of noradrenergic fibers on gan-glion cells is to inhibit their firing. There is some con-troversy concerning the role of noradrenergic fibers in the regulation of airway smooth muscle tone. There is no doubt, however, that adrenoceptors are present on bronchial smooth muscle and that epinephrine from the adrenal gland and drugs such as epinephrine and iso-proterenol produce bronchodilation of the airway.

Gastrointestinal Tract

The innervation of the gastrointestinal tract is complex. The myenteric and submucosal plexuses contain many interneurons. These possess a number of neurotransmit-ters and neuromodulators, including several peptides, such as enkephalins, substance P, and vasoactive intes-tinal peptide. Reflex activity within the plexuses regu-lates peristalsis and secretion locally. The effects of sym-pathetic and parasympathetic nerve stimulation are superimposed on this local neural regulation.

 

The myenteric and submucosal plexuses contain ganglion cells giving rise to excitatory cholinergic fibers that directly innervate the smooth muscle and gland cells of the gut. The sympathetic fibers that enter the gastrointestinal tract are postganglionic noradrenergic fibers, stimulation of which inhibits gut motility and gland secretion and contracts sphincters. Most of the noradrenergic fibers terminate either in blood vessels or on the cholinergic ganglionic cells of the intramural plexuses. These fibers alter gut motility by inhibiting acetylcholine release from the intramural nerves. Direct noradrenergic innervation of smooth muscle of the non-sphincter portion of the gut is sparse.

Salivary Glands

One exception to the generalization that the two sys-tems work in opposition to each other is secretion by the salivary glands; both sympathetic (noradrenergic) and parasympathetic (cholinergic) activation of these glands leads to an increase in the flow of saliva. However, the nature of the saliva produced by the two systems is qual-itatively different. The saliva produced by activation of the sympathetic system is a sparse, thick, mucinous se-cretion, whereas that produced by parasympathetic acti-vation is a profuse, watery secretion

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