Nitric oxide‐dependent release of vasodilator quantities of calcitonin gene‐related peptide from capsaicin‐sensitive nerves in rabbit skin

Abstract

1. Calcitonin gene-related peptide (CGRP) is a potent and long lasting vasodilator in the cutaneous microvasculature of many species including the rabbit. In this study we have investigated the role of nitric oxide in the release of endogenous CGRP, in response to capsaicin, in rabbit skin. 2. Cutaneous blood flow was measured in response to intradermally-injected agents by a multiple site 133Xenon clearance technique. 3. The increased blood flow induced by capsaicin (100 nmol/site) and CGRP (3 pmol/site) was totally inhibited by the CGRP antagonist CGRP(8-37) (1 nmol/site), whilst the increased blood flow induced by sodium nitroprusside (0.3, 1 and 3 nmol/site) was unaffected by CGRP(8-37). 4. The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 30 nmol/site) had no effect on the vasodilator response induced by CGRP, but significantly inhibited capsaicin-induced blood flow. The inhibitory effect of L-NAME on capsaicin-induced blood flow was reversed by intradermal L-arginine (300 nmol/site), whilst the inactive enantiomer D-NAME (30 nmol/site) and the alpha-adrenoceptor agonist phenylephrine (10 pmol/site), at a dose which had a similar effect to L-NAME on basal blood flow, had no effect on capsaicin-induced blood flow. 5. These results suggest that CGRP is the important vasodilator which is released from capsaicin-sensitive sensory nerves in rabbit skin and that the release of CGRP, but not its mechanism of vasodilator action, is nitric oxide-dependent in the rabbit cutaneous microvasculature.