Effects of nipradilol on alpha-adrenoceptor function in ocular arteries

The effects of nipradilol, a drug used in the treatment of glaucoma, on the contractions induced by noradrenaline and phenylephrine in isolated dog central retinal, external and internal ophthalmic arteries and pig ciliary arteries were investigated. In dog ocular arteries treated with oxyhemoglobin (1.6 x 10(-5) mol/l) to adsorb nitric oxide, noradrenaline (2 x 10(-8) to 10(-5) mol/l) produced a concentration-related contraction which was markedly inhibited by prazosin but not by yohimbine. Nipradilol (10(-9) to 10(-7) mol/l) slightly but significantly inhibited the noradrenaline-induced contraction in a concentration-related manner, but the inhibitory potency and efficacy were much less than those of prazosin. However, nipradilol inhibited the phenylephrine-induced contraction with a similar PA(2) value of prazosin. In pig ciliary arteries treated with oxyhemoglobin, noradrenaline-induced contraction was slightly inhibited by prazosin but markedly inhibited by yohimbine. Nipradilol, similarly to timolol, did not inhibit, but rather tended to potentiate, the contraction elicited by noradrenaline. The contraction induced by phenylephrine was significantly inhibited by prazosin and nipradilol. It is concluded that nipradilol acts as an alpha(1)-adrenoceptor antagonist (but not as an alpha(2)-adrenoceptor antagonist) in the ocular arteries, which may partially explain its ocular-pressure-lowering mechanism. Taken together with the results of our previous studies, the potencies of the nipradilol-induced vascular actions in ocular arteries are found to be in the following order: beta-adrenoceptor inhibition > alpha(1)-adrenoceptor inhibition falling dots direct vasodilation via a release of nitric oxide.