Stroke, Vol 25, 429-435, Copyright © 1994 by American Heart Association
E Morikawa, MA Moskowitz, Z Huang, T Yoshida, K Irikura and T Dalkara
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 spontaneously
hypertensive rats when administered intraperitoneally before and after MCA
occlusion. In this report we extend our findings (1) by examining the time
course of L-arginine on rCBF and pial vessel diameter under basal
conditions and on rCBF after MCA occlusion and (2) by reproducing the
protective effect of L-arginine on infarct volume when given intravenously
immediately after the onset of MCA occlusion in both normotensive and
hypertensive models of focal cerebral ischemia. METHODS: Changes in pial
vessel diameter (closed cranial window) and rCBF (laser-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 range of 80% of baseline. The
effects of infusing L-arginine (300 mg/kg for 10 minutes beginning 5
minutes after occlusion) were assessed on infarction volume in
Sprague-Dawley rats after proximal MCA occlusion and in spontaneously
hypertensive rats after common carotid artery plus distal MCA occlusion.
RESULTS: L-Arginine (300 mg/kg IV) elevated rCBF by 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 (> or = 30 mg/kg IV) increased blood flow distal to MCA
occlusion by 50%. These effects were sustained throughout the observation
period (70 to 105 minutes). Changes in mean arterial blood pressure were
not observed. L-Arginine (300 mg/kg IV) reduced infarction volume by 35%
and 28% in Sprague- Dawley and spontaneously hypertensive rats,
respectively, when examined 24 hours after vessel occlusion. CONCLUSIONS:
These studies extend our previous findings by demonstrating that exogenous
L-arginine induces sustained rCBF increases in normal brain as well as in a
marginally perfused brain region distal to MCA occlusion. Our data in
Sprague- Dawley rats support the conclusion that L-arginine-induced
increases in rCBF can decrease infarction volume. We conclude that nitric
oxide- mediated mechanisms increase rCBF and decrease infarction volume
after MCA occlusion in both normotensive and hypertensive animals.
ARTICLES
L-arginine infusion promotes nitric oxide-dependent vasodilation, increases regional cerebral blood flow, and reduces infarction volume in the rat
Neurosurgery Service, Massachusetts General Hospital, Boston 02114.
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