Sympathetic adrenergic nerves are found in the heart where they innervate the SA and AV nodes, conduction pathways, and myocytes.Sympathetic adrenergic fibers are also found innervating arteries and veins in the peripheral vasculature.These adrenergic nerves release the neurotransmitter, norepinephrine (NE), which binds to specific receptors in the target tissue. The heart is also innervated by parasympathetic cholinergic nerves derived from the vagus nerves.Acetylcholine (ACh) released by these fibers binds to muscarinic receptors in the target tissue.The vasculature in some organs of the body is innervated by either parasympathetic cholinergic fibers or by sympathetic cholinergic fibers. These nerves release ACh, which binds to muscarinic receptors on the smooth muscle and/or endothelium.
In the heart, NE released by sympathetic nerves preferentially binds to 1 adrenoceptors causing positive inotropy, chronotropy, and dromotropy.Postjunctional 2 adrenoceptor stimulation has similar cardiac effects and becomes increasingly important in heart failure because 1 adrenoceptors become down regulated. NE can also bind to 1 adrenoceptors on myocytes causing small increases in inotropy.Circulating catecholamines (NE and epinephrine) (not shown in diagram) released by the adrenal medulla also binds to these same alpha and beta adrenoceptors on the heart.
In blood vessels, NE preferentially binds 1 adrenoceptors to cause smooth muscle contraction and vasoconstriction. Similar responses occur when NE binds to postjunctional 2 receptors located on some blood vessels. NE can also bind to postjunctional 2 adrenoceptors which causes vasodilation (this can be observed during alpha adrenoceptor blockade), although this vasodilator effect of NE is relatively minor and overwhelmed by alpha adrenoceptor-mediated vasoconstriction. Circulating epinephrine (not shown in diagram) binds to the 2 adrenoceptors to cause vasodilation in some organs.
NE regulates its own release by acting upon prejunctional 2 (inhibits release) and 2 (facilitates release) adrenoceptors.
In the heart, ACh released by cholinergic nerves bind to a subclass of cholinergic receptors called M2 muscarinic receptors. This produces negative inotropy, chronotropy, and dromotropy in the heart. Prejunctional M2 receptor activation inhibits NE release and is one mechanism by which vagal stimulation overrides sympathetic stimulation in the heart.
In blood vessels, M2 receptors on the vascular endothelium are coupled to the formation of nitric oxide (NO) which causes vasodilation; however, ACh causes smooth muscle contraction through a smooth muscle M3 receptor when formation of NO is blocked. This latter finding has been used to assess coronary vascular dysfunction in humans in which NO production is diminished in diseased coronary arteries.
Some arterial blood vessels, for example in skeletal muscle, are innervated by sympathetic cholinergic nerves that release ACh and cause vasodilation. This may contribute to active hyperemia in skeletal muscle, particularly at the onset of exercise.
Neurotransmitter binding to the adrenergic and cholinergic receptors activates signal transduction pathways that that cause the observed changes in cardiac and vascular function.
Drugs are available for blocking adrenergic and cholinergic receptors. For example, beta-blockers are used in the treatment of angina, hypertension, arrhythmias, and heart failure. Alpha-blockers are used in treating hypertension. Muscarinic receptor blockers such as atropine are used to treat electrical disturbances (e.g., bradycardia and conduction blocks) associated with excessive vagal stimulation of the heart. Many of these adrenergic and cholinergic blockers are relatively selective for a specific receptor subtype.
