Topical ocular instillation of nitric oxide synthase inhibitors and intraocular pressure in rabbits.
OBJECTIVE
It has been reported that intravenous injection of the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl esther (L-NAME) causes a rapid decrease of intraocular pressure (IOP) in rabbits. This study investigates the effect of topical ocular application of different NOS inhibitors on a raise of IOP induced by an acute water intake (rabbit water loading model).


METHODS
Forty New Zealand (albino) male rabbits received randomly (within thirty minutes) in their right eye three 50 microliters installations of either 0.9% NaCl, 0.5% timolol maleate (beta-adrenoreceptor antagonist), 0.5% 7-nitroindazole (7-NI; NOS inhibitor), 0.5% L-NAME, or 0.5% 2-amino-5,6-dihydro-6-methyl-1,3,-thiazine (AMT; NOS inhibitor) before an oral water gavage (60 ml/kg). IOP was measured (TonoPen) before and after topical instillation (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 difference versus time (arbitrary units) was 527 +/- 284 for NaCl, 255 +/- 178 for timolol, 466 +/- 242 for 7-NI, 604 +/- 195 for L-NAME, and 394 +/- 202 for AMT. Values of AUC were only significantly lower (p < 0.05) in the timolol-treated group. In left eyes, no significant difference (p > 0.05) could be observed in values of AUC between groups.


CONCLUSIONS
Under the present experimental conditions (including concentration 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.
Fleischhauer
J C
JC
Laboratory of Ocular Pharmacology and Physiology, University Eye Clinic Basel, Mittlere Strasse 91, PO Box, CH-4012 Basel.
Liu
R
R
Elena
P P
PP
Flammer
J
J
Haefliger
I O
IO
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007191:Indazoles / Q000494:pharmacology; D007429:Intraocular Pressure / Q000187:drug effects* / Q000502:physiology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000502:physiology; D009883:Ophthalmic Solutions; D011817:Rabbits; D013843:Thiazines / Q000494:pharmacology; D013999:Timolol / Q000494:pharmacology
C093124:2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine; D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D007191:Indazoles; D009883:Ophthalmic Solutions; D013843:Thiazines; D013999:Timolol; D019001:Nitric Oxide Synthase; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester