Adrenergic Function

Overview of the Effects of Epinephrine

The adrenergic neurons influence many bodily functions, but the effects on circulation and respiration are among the most important. The effects of sympathetic

TABLE 16-3 -- Effects of sympathetic nervous system activation

Site of Action	Stimulation	Inhibition
Heart	Rate, conduction, contractility
Blood vessels	Vasoconstriction (skin, gut, liver, heart, kidney)	Vasodilation (skeletal muscle, heart, brain)
Respiration	Respiratory center
	Bronchodilation
Gastrointestinal tract	Sphincters	Smooth muscle
Genitourinary tract	Sphincters	Ureteral and uterine muscle
Metabolic and endocrine effects	Glycogenolysis (muscle, liver)	Insulin release (α stimulation or β1 antagonism)
	Lipolysis
	Gluconeogenesis
	Insulin release (β1 )
	Renin release
	ADH release
ADH, antidiuretic hormones or arginine vasopressin.

nervous stimulation on the body's physiology are designed to facilitate fight or flight ( Table 16-3 ). Ventilation is increased by a central effect on the ventilatory centers and by bronchodilation. Cardiac output is increased through an increase in the contractile force of the heart and the rate of contraction, and perfusion pressure for vital organs is increased by constriction of vessels to nonvital organs. Function of the gastrointestinal and genitourinary systems is decreased as a result of a relaxation of the smooth muscle in these organs and contraction of their sphincters. Gastrointestinal secretory activity is inhibited, and adrenal medullary output is increased. Metabolism is generally stimulated to provide more fuel for bodily function in the form of glucose and fatty acids.

The endogenous catecholamines, norepinephrine and epinephrine, possess α- and β-receptor agonistic activity. Norepinephrine has minimal β₂ -receptor activity, whereas epinephrine stimulates the β₁ - and β₂ -receptors ( Table 16-4 ). Fundamental differences exist between the infusion of exogenous catecholamines and release of endogenous catecholamines. For example, infused norepinephrine can elicit bradycardia, but when released in response to stress, it evokes tachycardia.

The physiologic responses mediated by α-adrenoceptors are wide ranging and important. α-Receptor-mediated activity is responsible for most of the sympathetically induced smooth muscle contraction throughout the body, including the ciliary muscle of the eye and vascular, bronchial, and ureteral smooth muscle.^[24] The gastrointestinal and genitourinary sphincter mechanisms are stimulated by α-adrenergic receptors. α-Receptor agonism also mediates sympathetic nervous system control of pancreatic insulin secretion. In the peripheral vasculature, postjunctional α₁ - and α₂ -receptors are found on arteries and veins and act to mediate vasoconstriction independent of nerve supply.

β-Receptor agonism appears to be primarily responsible for sympathetic stimulation of the heart, relaxation of vascular and bronchial smooth muscle, stimulation of renin secretion by the kidney, and several metabolic

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Psychological and physical stimuli may evoke different compensatory responses. Whereas public speaking activates the adrenal gland and the sympathetic nervous system, physical exercise elicits primarily a sympathetic response.^[29] The stress response should not be conceived of as a uniform response; it can vary in intensity and manifestations.

Blood Glucose

Catecholamines are released to mobilize glucose in the face of systemic hypoglycemia and to normalize glucose values, providing cells with energy. Overall, sympathetic nervous stimulation through β-receptor stimulation increases glycogenolysis in liver and muscle and liberates free fatty acids from adipose tissue, ultimately increasing blood glucose levels. In neonates, epinephrine plays an additional role in the exothermic breakdown of brown fat to maintain body temperature (i.e., nonshivering thermogenesis).

The α₂ - and β₂ -receptors also are present in the pancreas. α₂ -Receptor activation suppresses insulin secretion by pancreatic islets and inhibits lipolysis; blockade of these receptors may increase insulin release and may be associated with significant lowering of blood glucose levels. β-Receptor stimulation increases glucagon and insulin secretion.^[30]

Potassium Shift

Plasma epinephrine also regulates serum potassium concentration. β-Adrenergic stimulation can initiate transient hyperkalemia as potassium shifts out of hepatic cells with the glucose efflux produced by β₂ -adrenergic stimulation. This effect is followed by a more prolonged hypokalemia as β₂ -adrenergic stimulation drives potassium into red blood cells and muscle cells. Exogenously administered or endogenously released epinephrine stimulates the β₂ -receptors of red blood cells, activating adenylate cyclase and the sodium-potassium ATPase, driving potassium into cells. This leads to a reduction in serum potassium concentration and may contribute to the cardiac dysrhythmias accompanying MI and other stresses. β₂ -Adrenergic blockade has the theoretical advantage of inhibiting this potassium shift. However, the selective and nonselective β-blockers have been shown to be equivalent in protecting the postinfarction heart against arrhythmias. ^{[31] [32] [33] [34] [35]}