THE EFFECT OF NITRIC-OXIDE SYNTHASE INHIBITION ON INFARCT VOLUME AFTER REVERSIBLE FOCAL CEREBRAL-ISCHEMIA IN CONSCIOUS RATS

Background and Purpose: Previous in vitro and in vivo studies of the e ffects of nitric oxide synthase inhibition in the central nervous syst em have yielded conflicting results concerning the role of nitric oxid e in the events that lead to ischemic injury. In this study, we tested the hypothesis that preischemic inhibition of nitric oxide synthase i ncreases infarct volume after reversible focal cerebral ischemia in ra ts. Methods. N(G)-nitro-L-arginine methyl ester hydrochloride 15 mg/kg IV or an equivalent volume of saline was administered to adult Wistar rats 15 minutes before middle cerebral artery occlusion by the intral uminal suture method. After 2 hours of ischemia, the suture was withdr awn, and rats were allowed to survive for 3 days. Areas of infarction in 10 hematoxylin-eosin-stained sections were measured and used to det ermine infarct volume. Results: Administration of N(G)-nitro-L-arginin e methyl ester hydrochloride increased hemispheric infarct volume by 1 37% over control (60.9+/-30.5 to 144.3+/-19.6 mm3, P<.05; mean+/-SEM). Cortical and subcortical infarct volumes were increased by 176% (33.8 +/-21.9 to 93.3+/-15.2 mm3, P<.05) and 103% (25.1+/-9.4 to 51.0+/-5.5 mm3, P<.03), respectively. Conclusions: Nitric oxide synthase inhibiti on increases infarct volume and decreases the variability of the respo nse to middle cerebral artery occlusion in Wistar rats, a strain that is normally resistant to focal cerebral ischemic injury owing to exten sive collateralization. The mechanism of the deleterious effect of nit ric oxide synthase inhibition likely involves a more severe degree of blood flow reduction during and after middle cerebral artery occlusion , primarily by preventing the vasodilatory response of collateral vess els to proximal middle cerebral artery occlusion. Maintenance of nitri c oxide synthase activity during and after focal cerebral ischemia app ears to minimize ischemic injury.