Enhancement effect of carteolol on the clonidine-induced vasodilation of rat mesenteric arteries

Abstract

It has demonstrated that carteolol can increase the endothelium-dependent vasodilation induced by alpha-2 adrenergic agonist. In order to evaluate the effect of carteolol, and to clarify the mechanism, we examined the effects of 10 μ m carteolol on the vasodilation induced by increasing doses (10 −7−10−4) M) of clonidine in perfused rat mesenteric arteries preconstricted with 100 μ m phenylephrine. Clonidine elicited a dose-dependent vasodilation of the mesenteric arteries preconstricted with phenylephrine. Carteolol enhanced the vasodilation induced by higher doses (10 −5 and 10 −4 M) of clonidine, although carteolol itself exerted no direct vasodilating effect. On the other hand, 10 μ m propranolol or 10 μ m metoprolol did not augment the clonidine-induced vasodilation. In the presence of 100 μ m N G-monomethyl l-arginine (LNMMA), an analogue of l-arginine, the enhancement of the clonidineinduced vasodilation by carteolol was abolished. This inhibition by LNMMA was restored with 300 μ m l-arginine, but not with 300 μ m D-arginine. These results suggest that carteolol enhances the clonidine-induced vasodilation by an endothelial-related mechanism mediated by the release of endothelium-derived nitric oxide in resistance vessels.