Calcitonin gene-related peptide acts as a novel vasodilator neurotransmitter in mesenteric resistance vessels of the rat

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Abstract
Systemic blood pressure is controlled by changes in the resistance of the peripheral vascular bed for example in the mesenteric blood vessels1. The tone of peripheral blood vessels is primarily maintained by sympathetic vasoconstrictor nerves. Although vasodilator innervation has been identified in certain isolated elastic arteries2,3, it is not known whether vasodilator nerves contribute to the regulation of the peripheral resistance vessels. We present pharmacological evidence for the existence of nonadrenergic, non-cholinergic (NANC) vasodilator nerves in the mesenteric resistance vessel of the rat and that the resistance is controlled by not only sympathetic vasoconstrictor nerves but also NANC vasodilator nerves. We also show that the neurogenic vasodilation was selectively abolished by depleting endogenous calcitonin gene-related peptide (CGRP), a potent vasodilator neuropeptide4,5, from perivascular nerves. This indicates that CGRP is a novel vasodilator neurotransmitter and may play a role in control of the total peripheral resistance of systemic circulation through a local reflex mechanism.