Low dose L-NAME reduces infarct volume in the rat MCAO/reperfusion model.
In a variety of recent studies, inhibitors of nitric oxide (NO) synthesis have ameliorated neuronal injury during permanent focal cerebral ischemia, suggesting that NO may contribute to ischemic damage. In other studies, however, these inhibitors increased infarct volume during permanent middle cerebral artery occlusion (MCAO). One complication in these studies was that high-dose NO synthase inhibitors increased mean arterial blood pressure (MAP) by 20-30 mm Hg. Thus, it is possible that variations in the effects of NO synthesis inhibitors on infarct volume could be related to effects of these inhibitors on MAP and cerebral perfusion during or after ischemia. The present study compared the effects of control (Ringer's lactate solution) versus low-dose NO inhibition (0.1 mg/kg bolus followed by 0.01 mg/kg/min) on cerebral infarct volume using L-NAME (NG-nitro-L-arginine methyl ester) administered during a 1-h baseline period, 3-h of MCAO, and 2 h of reperfusion in the spontaneously hypertensive rat. Infarct volume was determined using the TTC (2,3,5-triphenyltetrazolium chloride) method performed 5 h after onset of occlusion. L-NAME reduced infarct volume by 55%. In the control group (n = 7), infarct volume measured 116 +/- 4 (SEM) mm3 which was 29 +/- 1% of the left hemispheric volume (400.5 +/- 0.3 mm3). In the L-NAME group (n = 7), infarct volume measured 53 +/- 8 mm3 which was only 13 +/- 2% of the left hemispheric volume (400.4 +/- 0.5 mm3).(ABSTRACT TRUNCATED AT 250 WORDS)
Ashwal
S
S
Department of Pediatrics, Loma Linda University School of Medicine, California.
Cole
D J
DJ
Osborne
T N
TN
Pearce
W J
WJ
D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001157:Arterial Occlusive Diseases / Q000473:pathology; D002539:Cerebral Arterial Diseases / Q000473:pathology; D002544:Cerebral Infarction / Q000188:drug therapy*; D002560:Cerebrovascular Circulation; D008954:Models, Biological; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D051381:Rats; D011918:Rats, Inbred SHR; D015424:Reperfusion
D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester