Mechanism of the vasodilator action of calcitonin gene‐related peptide in conscious rats

The aim of this study was to investigate whether the hypotensive effect of rat α‐calcitonin gene‐related peptide (αCGRP) in conscious rats is mediated by endothelium‐derived nitric oxide (NO) or the opening of adenosine 5′‐triphosphate (ATP)‐sensitive potassium (K_ATP) channels. Dose‐mean arterial pressure (MAP)‐response curves of αCGRP 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. αCGRP and nitroprusside produced dose‐dependent reductions in MAP which were potentiated by phenylephrine. Both l‐NAME and d‐NAME attenuated the depressor response to αCGRP but not nitroprusside. 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 αCGRP‐induced reductions in MAP. It is concluded that the hypotensive effects of αCGRP are partially mediated via endothelium‐derived NO but not via the opening of K_ATP channels. 1992 British Pharmacological Society