Importance of the smooth vascular cell

The tone of vascular smooth-muscle cells is governed by the autonomic nervous system and by the endothelium in tightly regulated
control networks. Autonomic neurons enter the blood vessel medial layer from the adventitia and modulate vascular smooth-muscle
cell tone in response to baroreceptors and chemoreceptors within the aortic arch and carotid bodies and in response to
thermoreceptors in the skin. These regulatory components include rapidly acting reflex arcs modulated by central inputs that

respond to sensory inputs (olfactory, visual, auditory, and tactile) as well as emotional stimuli. Three classes of nerves mediate
autonomic regulation of vascular tone: sympathetic, whose principal neurotransmitters are epinephrine and norepinephrine;
parasympathetic, whose principal neurotransmitter is acetylcholine; and nonadrenergic/noncholinergic, which include two subgroups
—nitrergic, whose principal neurotransmitter is NO, and peptidergic, whose principal neurotransmitters are substance P, vasoactive
intestinal peptide, calcitoningene-related peptide, and ATP.
Each of these neurotransmitters acts through specific receptors on the vascular smooth-muscle cell to modulate intracellular calcium
and, consequently, contractile tone. Norepinephrine activates receptors, and epinephrine activates and receptors (adrenergic
receptors); in most blood vessels, norepinephrine activates postjunctional 1 receptors in large arteries and 2 receptors in small
arteries and arterioles, leading to vasoconstriction. Most blood vessels express 2-adrenergic receptors on their vascular smoothmuscle
cells and respond to agonists by cyclic AMP–dependent relaxation. Acetylcholine released from parasympathetic neurons
binds to muscarinic receptors (of which there are five subtypes, M1–5) on vascular smooth-muscle cells to yield vasorelaxation. In
addition, NO stimulates presynaptic neurons to release acetylcholine, which can stimulate the release of NO from the endothelium.
Nitrergic neurons release NO produced by neuronal NO synthase, which causes vascular smooth-muscle cell relaxation via the cyclic
GMP–dependent and –independent mechanisms described above. The peptidergic neurotransmitters all potently vasodilate, acting
either directly or through endothelium-dependent NO release to decrease vascular smooth-muscle cell tone. For the detailed
molecular physiology of the autonomic nervous system, see Chap. 375.
The endothelium modulates vascular smooth-muscle tone by the direct release of several effectors, including NO, prostacyclin,
hydrogen sulfide, and endothelium-derived hyperpolarizing factor, all of which cause vasorelaxation, and endothelin, which causes
vasoconstriction. The release of these endothelial effectors of vascular smooth-muscle cell tone is stimulated by mechanical (shear
stress, cyclic strain, etc.) and biochemical mediators (purinergic agonists, muscarinic agonists, peptidergic agonists), with the
biochemical mediators acting through endothelial receptors specific to each class. In addition to these local paracrine modulators of
vascular smooth-muscle cell tone, circulating mediators can affect tone, including norepinephrine and epinephrine, vasopressin,
angiotensin II, bradykinin, and the natriuretic peptides (ANP, BNP, CNP, and DNP), as discussed above.