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Nitric oxide‐dependent release of vasodilator quantities of calcitonin gene‐related peptide from capsaicin‐sensitive nerves in rabbit skin
Author(s) -
Hughes S.R.,
Brain S.D.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb14752.x
Subject(s) - calcitonin gene related peptide , capsaicin , nitric oxide , vasodilation , chemistry , calcitonin , sodium nitroprusside , endocrinology , medicine , nitric oxide synthase , phenylephrine , pharmacology , neuropeptide , receptor , biochemistry , blood pressure
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 133 Xenon 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 N G ‐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 α‐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 capsaicinsensitive 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.