title: Nitric oxide synthase inhibition by L-NAME during repetitive focal cerebral ischemia in rabbits.
abstract: The effects of nitric oxide synthase inhibition on brain acidosis, regional cortical blood flow (rCBF), and NADH redox state were examined using in vivo fluorescence imaging during four 15-min periods of moderate focal cerebral ischemia, each separated by three 5-min reperfusion periods followed by a final 3-h reperfusion period. Fasted rabbits under 1.5% halothane were divided into six groups of seven animals each: nonischemic controls, ischemic controls, and the following drug groups receiving NG-nitro-L-arginine methyl ester (L-NAME) intravenously 20 min before repetitive ischemia (as follows: 0.1 mg/kg, 1 mg/kg, 10 mg/kg, and 1 mg/kg + 5 mg/kg L-arginine). L-NAME at 0.1 and 1 mg/kg prevented the development of significant brain acidosis throughout the four ischemic insults. L-NAME at 10 mg/kg reduced preischemic rCBF by 21% (P < 0.05) and did not mitigate brain acidosis after the third and fourth ischemic insults. Brain intracellular pH returned toward baseline after the 3-h final reperfusion in all groups. NADH redox state was significantly (P < 0.05) elevated from baseline controls in all groups during the last three ischemic insults. During the final reperfusion period, NADH redox state returned toward baseline values only in the 0.1 mg/kg L-NAME and ischemic control group. In conclusion, low-dose L-NAME attenuated brain acidosis independent from rCBF changes during intermittent, moderate focal cerebral ischemia.
authors.affiliation: Neurosurgical Research Laboratory, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Anderson
authors.forename: F B
authors.initials: FB
authors.lastname: Meyer
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002560:Cerebrovascular Circulation; D005453:Fluorescence; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000201:enzymology* / Q000503:physiopathology; D009243:NAD / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010084:Oxidation-Reduction; D011817:Rabbits
chemical_list: D009243:NAD; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester