The effect of nitric oxide synthase inhibition on infarct volume after reversible focal cerebral ischemia in conscious rats

Abstract

Background and Purpose: Previous in vitro and in vivo studies of the effects of nitric oxide synthase inhibition in the central nervous system have yielded conflicting results concerning the role of nitric oxide in the events that lead to ischemic injury. In this study, we tested the hypothesis that preischemic inhibition of nitric oxide synthase increases infarct volume after reversible focal cerebral ischemia in rats. Methods: NG-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 intraluminal suture method. After 2 hours of ischemia, the suture was withdrawn, and rats were allowed to survive for 3 days. Areas of infarction in 10 hematoxylin-eosin-stained sections were measured and used to determine infarct volume. Results: Administration of NG-nitro-l-arginine methyl ester hydrochloride increased hemispheric infarct volume by 137% over control (60.9 ± 30.5 to 144.3 ± 19.6 mm3, P