THE CONTRIBUTION OF CALCITONIN GENE-RELATED PEPTIDE (CGRP) TO NEUROGENIC VASODILATOR RESPONSES

The neuropeptide calcitonin gene-related peptide (CGRP) is a potent vasodilator in the microcirculation of many tissues including the skin and joint. In order to elucidate the mechanism of endogenous CGRP release, we have used a multiple site Xe-133 clearance technique to measure local blood flow changes in response to agents injected intradermally in the rabbit. Capsaicin (100 nmol/site) and human alphaCGRP (3 pmol/site) stimulated similar increases in blood flow and, in both cases, the effect was totally abolished by the CGRP antagonist, CGRP8-37 (1 nmol/site). By contrast, the nitric oxide synthase inhibitor L-nitro arginine methyl ester (L-NAME, 30 nmol/site) had little effect on human alphaCGRP-induced vasodilation, but caused significant inhibition of the response to capsaicin (p<0.05). These results show that increased blood flow in rabbit skin caused by exogenous CGRP is independent of nitric oxide. In addition, however, they suggest that nitric oxide is required for either the release of endogenous CGRP from capsaicin-sensitive nerves or its subsequent activity.