Pharmacology and Physiology of Perivascular Nerves Regulating Vascular Function

The rat mesenteric artery is innervated by nonadrenergic noncholinergic (NANC) vasodilator nerves in which calcitonin gene-related peptide (CGRP), a potent vasodilator peptide, acts as a vasodilator transmitter. The inhibition of CGRPergic nerve function potentiates a vasoconstrictor response mediated by the sympathetic adrenergic nerve, suggesting that CGRPergic nerves inhibit adrenergic function and play a role in the regulation of mesenteric vascular tone. In contrast, norepinephrine released from adrenergic nerves presynaptically inhibits neurotransmission of CGRPergic nerves. Thus, both nerves reciprocally control the vascular tone. Pathophysiological studies have shown that an age-related decrease in CGRPergic nerve-mediated vasodilation, neurogenic CGRP release and CGRP mRNA levels in the dorsal root ganglia are found in spontaneously hypertensive rats (SHR), indicating a reduced function of CGRPergic nerves. Long-term treatment with angiotensin converting enzyme inhibitor and angiotensin II-receptor antagonist restores the reduced function of CGRPergic nerves, suggesting the involvement of angiotensin II in the malfunction of CGRPergic nerves in SHR.