Prostaglandins Mediate the Ocular Hypotensive Action of the Angiotensin Converting Enzyme Inhibitor MK-422 (Enalaprilat) in African Green Monkeys

Abstract

MK-422 (enalaprilat) (0.0005-0.5%) significantly reduced intraocular pressure (IOP) in African Green monkeys. Studies utilizing unilateral instillation of MK-422 and its inactive R-isomer indicated a local site of action within the eye which is dependent upon inhibition of angiotensin converting enzyme, also known as kininase II. Tonography showed a small increase (21%) in conventional aqueous humor outflow facility which did not entirely account for the IOP lowering effect of MK-422. Pretreatment with indomethacin or pilocarpine specifically attenuated the ability of MK-422 to lower IOP suggesting that biosynthesis of prostaglandins and uveoscleral outflow pathways are important in mediating the ocular hypotension. The data indicate that MK-422 may lower IOP in monkeys by virtue of its ability to prevent the breakdown of bradykinin and thereby promote the formation of endogenous prostaglandins in the eye.