Time dependence of effect of nitric oxide synthase inhibition on cerebral ischemic damage

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
F ZhangC Iadecola

Abstract

Nitric oxide, a potent vasodilator and an inhibitor of platelet aggregation, may be beneficial in the early stages of focal cerebral ischemia as it may facilitate collateral blood flow to the ischemic territory. Accordingly, the effect of inhibition of nitric oxide synthesis on cerebral ischemic damage may vary depending on the timing of the inhibition relative to the induction of ischemia. We therefore studied the time course of the effect of nitric oxide synthesis inhibition on focal cerebral ischemic damage. The middle cerebral artery was permanently occluded in spontaneously hypertensive rats and the nitric oxide synthase (NOS) inhibitor nitro-L-arginine methyl ester (L-NAME) was administered systemically (3 mg/kg) < 5 min or 2, 3, or 6 h later. Arterial pressure, rectal temperature, plasma glucose, and hematocrit were monitored. Infarct volume was determined on thionin-stained sections 24 h after induction of ischemia. NOS activity was determined in cerebellum from the conversion of L-[3H]arginine to L-[3H]citrulline. Administration of L-NAME < 5 min after arterial occlusion increased the infarct volume by 23 +/- 14% (mean +/- SD; p < 0.05, analysis of variance), while administration of L-NAME at 2 or 6 h did not affect th...Continue Reading

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