Roles of constitutive nitric oxide synthase in postischemic rat retina.

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Abstract

PURPOSE: Nitric oxide is a reactive species that could be protective or destructive to the retina depending on the stage of the evolving ischemic process. This study was conducted to obtain a better understanding of the roles of constitutive nitric oxide synthase (cNOS) during reperfusion after ischemia in rat retina. METHODS: Retinal ischemia was induced for 60 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, NG-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 by the thickness of the retinal layers. Retinal circulation and vessel diameter 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 24 hours until the final measurement at 96 hours of reperfusion. nNOS mRNA decreased to nearly undetectable levels during the same measurement periods. L-NNA treatment enhanced reduction of a- and b-wave amplitudes and increased thinning of the inner retina in postischemic eyes. Retinal mean circulation time was markedly prolonged in L-NNA-treated postischemic eyes. Arterial mean transit times were 2.1-fold and 4.5-fold longer in L-NNA-treated postischemic 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 retinal damage after ischemia-reperfusion and alters postischemic retinal circulation. Nitric oxide may play an important role in protecting the retina from ischemic injury, possibly by preventing postischemic hypoperfusion.