Roles of constitutive nitric oxide synthase in postischemic rat retina

PURPOSE. Nitric oxide is a reactive species that could be protective or des tructive to the retina depending on the stage of the evolving ischemic proc ess. This study was conducted to obtain a better understanding of the roles of constitutive nitric oxide synthase (cNOS) during reperfusion after isch emia in rat retina. METHODS. Retinal ischemia was induced for GO minutes in Sprague-Dawley rats by ligating the optic nerve. Gene expression for endothelial and neuronal nitric oxide synthases (eNOS and nNOS) was studied by reverse transcription -polymerase chain reaction (RT-PCR). to inhibit cNos N-G-nitro-L-arginine ( L-NNA) was injected intraperitoneally four times (every 6 hours) beginning 2 hours after reperfusion, for a total dose of 80 mg/kg. Retinal damage was assessed by the rate of a- and b-wave recovery on electroretinograms and b y the thickness of the retinal layers. Retinal circulation and vessel diame ter were evaluated by the dye-dilution technique. RESULTS. After ischemia ended, eNOS mRNA initially decreased until 6 hours, then increased to a peak at 12 hours. and decreased progressively beyond 2 4 hours until the final measurement at 96 hours of reperfusion. nNOS mRNA d ecreased to nearly undetectable levels during the same measurement periods. L-NNA treatment enhanced reduction of a- and b-wave amplitudes and increas ed thinning of the inner retina in postischemic eyes. Retinal mean circulat ion time was markedly prolonged in L-NNA-treated postischemic eyes. Arteria l mean transit times were 2.1-fold and 4.5-fold longer in L-NNA-treated pos tischemic eyes than in L-NNA-treated nonischemic eyes and in D-NNA-treated postischemic eyes, respectively. CONCLUSIONS. This study shows that postischemic inhibition of NOS worsens r etinal damage ischemia-reperfusion and alters postischemic retinal circulat ion. Nitric oxide may play an important role in protecting the retina from ischemic injury, possibly by preventing postischemic hypoperfusion.