ENHANCEMENT EFFECT OF CARTEOLOL ON THE CLONIDINE-INDUCED VASODILATIONOF RAT MESENTERIC-ARTERIES

It has demonstrated that carteolol can increase the endothelium-depend ent vasodilation induced by alpha-2 adrenergic agonist. In order to ev aluate the effect of carteolol, and to clarify the mechanism, we exami ned the effects of 10 mu M carteolol on the vasodilation induced by in creasing doses (10(-7)-10(-4) M) of clonidine in perfused rat mesenter ic arteries preconstricted with 100 mu M phenylephrine. Clonidine elic ited a dose-dependent vasodilation of the mesenteric arteries preconst ricted with phenylephrine. Carteolol enhanced the vasodilation induced by higher doses (10(-5) and 10(-4) M) of clonidine, although carteolo l itself exerted no direct vasodilating effect. On the other hand, 10 mu M propranolol or 10 mu M metoprolol did not augment the clonidine-i nduced vasodilation. In the presence of 100 mu M N-G-monomethyl L-argi nine (LNMMA), an analogue of L-arginine, the enhancement of the clonid ine-induced vasodilation by carteolol was abolished. This inhibition b y LNMMA was restored with 300 mu M L-arginine, but not with 300 mu 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.