MECHANISM OF THE VASODILATOR ACTION OF CALCITONIN GENE-RELATED PEPTIDE IN CONSCIOUS RATS

1 The aim of this study was to investigate whether the hypotensive effect of rat alpha-calcitonin gene-related peptide (alpha-CGRP) in conscious rats is mediated by endothelium-derived nitric oxide (NO) or the opening of adenosine 5'-triphosphate (ATP)-sensitive potassium (K(ATP)) channels. 2 Dose-mean arterial pressure (MAP)-response curves of alpha-CGRP were examined in the presence of vehicle, phenylephrine, K(ATP) channel antagonist glibenclamide or NO synthase inhibitors, N(G)-nitro-L-arginine methyl ester (L-NAME) and N(G)-nitro-D-arginine methyl ester (D-NAME). Dose-MAP-response curves for sodium nitroprusside were also constructed in the presence and absence Of L-NAME and D-NAME. 3 Alpha-CGRP and nitroprusside produced dose-dependent reductions in MAP which were potentiated by phenylephrine. Both L-NAME and D-NAME attenuated the depressor response to alpha-CGRP but not nitroprusside. 4 Dose-MAP-response curves for pinacidil, a K(ATP)-channel activator. were also examined in the presence of glibenclamide or vehicle. Glibenclamide attenuated pinacidil- but not alpha-CGRP-induced reductions in MAP. 5 It is concluded that the hypotensive effects of alpha-CGRP are partially mediated via endothelium-derived NO but not via the opening of K(ATP) channels.