Involvement of nitric oxide in the ocular hypotensive action of nipradilol

PURPOSE: To evaluate the role of nitric oxide (NO) in the mechanism of the ocular hypotensive action of nipradilol, a beta-blocker with alpha( 1)-blocking activity. METHODS: Change in intraocular pressure (IOP) of albino rabbits was measured after a single application of carboxy-PTIO (c-PTIO), an NO trapping agent. Next, IOP change was measured every hour for 5 hours after the instillation of 0.25% nipradilol into one of the eyes with and without c-PTIO pretreatment of both eyes. IOP change induced by desnitro-nipradilol was also examined. The outflow facility and uveoscleral outflow were determined by two-level constant pressure and anterior chamber perfusion methods before and at 3 hours after the application of nipradilol with and without c-PTIO pretreatment. RESULTS: Topical administration of c-PTIO showed no significant effect on IOP. Unilateral instillation of nipradilol reduced IOP significantly compared with control eyes with a maximum reduction of 3.6 mmHg and effect duration of 3 hours. Pretreatment with c-PTIO partially inhibited the reduction during an earlier period (1 approximately 2 hours) and completely at 3 hours. IOP change by desnitro-nipradilol was similar to that by nipradilol with c-PTIO pretreatment. Nipradilol increased both outflow facility and uveoscleral outflow at 3 hours, whereas pretreatment with c-PTIO inhibited both of these outflows. CONCLUSIONS: Results indicate that ocular hypotensive action by nipradilol during the relatively late period may be mainly due to enhancement of aqueous humor outflow by NO at least in the rabbits.