Oculohypotensive effect of angiotensin-converting enzyme inhibitors in acute and chronic models of glaucoma

We have studied the effects of various angiotensin-converting enzyme (ACE) inhibitors on intraocular pressure (IOP) of rabbits with experimentally ind uced ocular hypertension and their mechanism of action. Acute ocular hypert ension was induced by infusion of 5% glucose (15 ml/kg) through marginal ea r vein, whereas chronic glaucoma was induced by injection of a-chymotrypsin into the posterior chamber of the eye. IOP was measured by tonometer. All ACE inhibitors were instilled topically in the eye in a sterile solution. T he effect of ACE inhibitors also was studied on serum cholinesterase (true and pseudo) and the enzyme ACE in vitro. Enalaprilat, ramiprilat, and fosin opril produced a time-dependent decrease of IOP in both acute and chronic m odels of ocular hypertension in rabbits. The decrease in IOP was observed f or >4 h, and the extent of decrease was comparable to that with both piloca rpine and betaxolol. Prodrugs enalapril and ramipril failed to produced any change in IOP. Losartan also produced a significant decrease in IOP in the chronic model of ocular hypertension in rabbits. All the three ACE inhibit ors were found to inhibit ACE activity in aqueous humor. The enzyme choline sterase was found to be inhibited by enalaprilat, ramiprilat, and fosinopri l. However, atropine did not alter the IOP-lowering effect of enalaprilat i n rabbits. Indomethacin pretreatment produced slight but significant inhibi tion of the IOP-lowering effect of enalaprilat in rabbits. Our data suggest that ACE inhibitors enalaprilat, ramiprilat, and fosinopril produce a sign ificant ocular hypotensive effect in acute and chronic models of ocular hyp ertension in rabbits. Inhibition of ACE in aqueous humor, and in ocular tis sues, resulting in reduced angiotensin II formation, could be one of the ma jor mechanisms responsible for the IOP reduction by ACE inhibitors in rabbi ts.