Calcitonin gene-related peptide is the endogenous mediator of nonadrenergic-noncholinergic vasodilation in rat mesentery.

In the isolated perfused rat mesenteric vascular bed pretreated with guanethidine and precontracted with methoxamine, periarterial nerve stimulation elicited a frequency-dependent and endothelium-independent vasodilation. The sustained vasodilation was slow-onset and reversible. It was resistant to propranolol or atropine but sensitive to tetrodotoxin and capsaicin suggesting that this is a nonadrenergic-noncholinergic vasodilation and is a neurogenic response. The vasodilation was abolished by anti-serum against calcitonin-gene related peptide (CGRP) in a concentration-dependent manner. These data suggest that the non-adrenergic-noncholinergic vasodilation is mediated by endogenous CGRP released from the primary sensory nerve terminals upon electrical stimulation. In addition to the vasodilator action, CGRP also inhibited nerve stimulation-induced and norepinephrine-induced vasoconstriction at extremely low concentrations. The inhibitory action of CGRP appeared to be mediated by postsynaptic mechanisms inasmuch as evoked norepinephrine release was not affected by CGRP when the vasoconstriction produced by norepinephrine or periarterial nerve stimulation was attenuated greatly by CGRP. These observations suggest that the vascular tone of the resistance vessels can be regulated by primary sensory nerve-derived CGRP.