Prostaglandins mediate the ocular hypotensive action of the angiotensin converting enzyme inhibitor MK-422 (enalaprilat) in African green monkeys.
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.
Lotti
V J
VJ
Department of New Lead Pharmacology, Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania.
Pawlowski
N
N
D000287:Administration, Topical; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002521:Cercopithecus / Q000502:physiology*; D002522:Chlorocebus aethiops / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D015773:Enalaprilat / Q000494:pharmacology*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D009798:Ocular Hypertension / Q000188:drug therapy*; D010862:Pilocarpine / Q000008:administration & dosage / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis / Q000502:physiology*; D012590:Sclera / Q000502:physiology; D014602:Uvea / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D011453:Prostaglandins; D010862:Pilocarpine; D015773:Enalaprilat; D007213:Indomethacin