NITRIC OXIDE-DEPENDENT AND OXIDE-INDEPENDENT HYPEREMIA DUE TO CALCITONIN-GENE-RELATED PEPTIDE IN THE RAT STOMACH

1 Calcitonin gene-related peptide (CGRP) potently enhances mucosal blo od flow in the rat stomach. The aim of this study was to examine wheth er CGRP also dilates extramural arteries supplying the stomach and whe ther the vasodilato; action of CGRP involves nitric oxide (NO). 2 Rat CGRP-alpha (0.03-1 nmol kg-1, i.v.) produced a dose-dependent increase in blood flow through the left gastric artery (LGA) as determined by an ultrasonic transit time technique in urethane-anaesthetized rats. B lockade of NO synthesis by NG-nitro-L-arginine methyl ester (L-NAME, 2 0 and 60 mumol kg-1, i.v.) significantly reduced basal blood flow (BF) in the LGA and attenuated the hyperaemic activity of CGRP by a factor of 2.8-4. D-NAME tended to enhance basal BF in the LGA but had no inf luence on the dilator activity of CGRP. The ability of vasoactive inte stinal polypeptide to increase left gastric arterial blood flow remain ed unaltered by L-NAME. 3 L-NAME (20 and 60 mumol kg-1, i.v.) evoked a prompt and sustained rise of mean arterial blood pressure (MAP) and c aused a slight decrease in the hypotensive activity of CGRP. In contra st, D-NAME induced a delayed and moderate increase in MAP and did not influence the hypotensive activity of CGRP. 4 Rat CGRP-alpha dilated t he isolated perfused bed of the rat LGA precontracted with methoxamine and was 3 times more potent in this respect than rat CGRP-beta. The d ilator action of rat CGRP-alpha in this preparation was not affected b y L-NAME or D-NAME (40 mum). 5 L-NAME (60 mumol kg-1, i.v.) reduced ga stric mucosal blood flow as assessed by laser Doppler flowmetry and di minished the hyperaemic activity of rat CGRP-alpha in the gastric muco sa by a factor of 4.5, whereas D-NAME was without effect. 6 These data show that CGRP is a potent dilator of mucosal and extramural resistan ce vessels in the rat stomach. Its dilator action involves both NO-dep endent and NO-independent mechanisms.