Topical ocular instillation of nitric oxide synthase inhibitors and intraocular pressure in rabbits

Purpose: It has been reported that intravenous injection of the nitric oxid e synthase (NOS) inhibitor N-G-nitro-L-arginine methyl esther (L-NAME) caus es a rapid decrease of intraocular pressure (IOP) in rabbits. This study in vestigates the effect of topical ocular application of different NOS inhibi tors on a raise of IOP induced by an acute water intake (rabbit water loadi ng model). Methods: Forty New Zealand (albino) male rabbits received randomly (within thirty minutes) in their right eye three 50 mul installations of either 0.9 % NaCl, 0.5% timolol maleate (beta -adrenoreceptor antagonist), 0.5% 7-nitr oindazole (7-NI; NOS inhibitor), 0.5% L-NAME, or 0.5% 2-amino-5,6-dihydro-6 -methyl-1,3,-thiazine thiazine (AMT; NOS inhibitor) before an oral water ga vage (60 ml/kg). IOP was measured (TonoPen (TM)) before and after topical i nstillation (time 0), and then 15, 30, 60, 90, and 120 minutes after water intake. Results: In right eyes, the area under the curve (AUC) of the IOP differenc e versus time (arbitrary units) was 527 +/- 284 for NaCl, 255 +/- 178 for t imolol, 466 +/- 242 for 7-NI, 604 +/- 195 for L-NAME, and 394 +/- 202 for A MT. Values of AUC were only significantly lower (p <0.05) in the timolol-tr eated group. In left eyes, no significant difference (p > 0.05) could be ob served in values of AUC between groups. Conclusions: Under the present experimental conditions (including concentra tion and bioavailability of the drugs used), topical application of the NOS inhibitors 7-NI, L-NAME, and AMT does not prevent an IOP increase induced by water intake in rabbits.