L-ARGININE INFUSION PROMOTES NITRIC OXIDE-DEPENDENT VASODILATION, INCREASES REGIONAL CEREBRAL BLOOD-FLOW, AND REDUCES INFARCTION VOLUME IN THE RAT

Background and Purpose We previously reported that L-arginine infusion increased pial vessel diameter by nitric oxide-dependent mechanisms, improved regional cerebral blood flow (rCBF) distal to middle cerebral artery (MCA) occlusion, and reduced infarction volume in spontaneousl y hypertensive rats when administered intraperitoneally before and aft er MCA occlusion. In this report we extend our findings (1) by examini ng the time course of L-arginine on rCBF and pial vessel diameter unde r basal conditions and on rCBF after MCA. occlusion and (2) by reprodu cing the protective effect of L-arginine on infarct volume when given intravenously immediately after the onset of MCA occlusion in both nor motensive and hypertensive models of focal cerebral ischemia. Methods Changes in pial vessel diameter (closed cranial window) and rCBF (lase r-Doppler flowmetry) were measured over time after L-arginine infusion into anesthetized Sprague-Dawley rats, rCBF was also measured distal to MCA occlusion in a brain region showing rCBF reductions in the rang e of 80% of baseline. The effects of infusing L-arginine (300 mg/kg fo r 10 minutes beginning 5 minutes after occlusion) were assessed on inf arction volume in Sprague-Dawley rats after proximal MCA occlusion and in spontaneously hypertensive rats after common carotid artery plus d istal MCA occlusion. Results L-Arginine (300 mg/kg IV) elevated rCBF b y 20% when measured in the dorsolateral cortex of Sprague-Dawley rats and caused L-nitroarginine-methyl ester-inhibitable increases in pial vessel diameter. L-Arginine (greater than or equal to 30 mg/kg IV) inc reased blood flow distal to MCA occlusion by 50%. These effects were s ustained throughout the observation period (70 to 105 minutes). Change s in mean arterial blood pressure were not observed. L-Arginine (300 m g/kg IV) reduced infarction volume by 35% and 28% in Sprague-Dawley an d spontaneously hypertensive rats, respectively, when examined 24 hour s after vessel occlusion. Conclusions These studies extend our previou s findings by demonstrating that exogenous L-arginine induces sustaine d rCBF increases in normal brain as well as in a marginally perfused b rain region distal to MCA occlusion. Our data in Sprague-Dawley rats s upport the conclusion that L-arginine-induced increases in rCBF can de crease infarction volume. We conclude that nitric oxide-mediated mecha nisms increase rCBF and decrease infarction Volume after MCA occlusion in both normotensive and hypertensive animals.