Potentiation of the depressor effect of acetylcholine by carvedilol

Carvedilol, a beta‐1,2 and alpha‐1 adrenoceptor blocker was explored in anesthetized rats in which systolic pressure was measured to determine if it enhances the vasodilator effect of single doses of acetylcholine (0.1, 0.15, 0.2, 0.25, 0.5 ug) by enhancing the availability of nitric oxide. At a maximal cumulative dose(1.364±0.228mg/kg) carvedilol potentiated the depressor effect of acetylcholine by 32‐15% (lowest to highest dose, P<0.01‐0.001). This effect was annulled by prevention of nitric oxide synthesis with nitro‐L‐arginine (15mg/kg) and restoration of the baseline systolic pressure with an infusion of nitroglycerin, a nitric oxide donor. Giving this treatment before carvedilol also prevented its potentiation of acetylcholine effect. Carvedilol may partly enhance the depressor effect of acetylcholine by annulling the reflexly‐mediated sympathetic compensation for the hypotension through its alpha‐1 adrenoceptor blockade. Pretreatment with phenoxybenzamine, a blocker of alpha‐1,2 adrenoceptors and an infusion of angiotensin II to restore basal systolic pressure to baseline had minimal effect on the depressor action of acetylcholine. This was also true with pretreatment with propranolol. It is concluded that carvedilol potentiated the depressor effect of acetylcholine essentially by enhancing the synthesis of nitric oxide. Supported by the American University of Beirut.