Inhibition of nitric oxide synthase with 7-nitroindazole does not modify early metabolic recovery following focal cerebral ischemia in rats.
Nitric oxide has been strongly implicated in the development of tissue infarction in response to focal cerebral ischemia. Nitric oxide and its derivatives can inhibit components of the electron transport chain, providing a likely target for these substances in ischemic and post-ischemic brain. Lactate content is increased during post-ischemic reperfusion in tissue destined to become infarcted, consistent with impairment of mitochondrial respiration. To investigate the possible involvement of nitric oxide in generating these changes, we have tested the effect of 7-nitroindazole, a nitric oxide synthase (NOS) inhibitor, on the content of lactate and other metabolites during early reperfusion following temporary focal ischemia. This treatment inhibited total NOS by approximately 50%. However, the treatment did not significantly affect the marked increases in lactate in post-ischemic brain nor did it alter the recovery of other energy-related metabolites. These findings indicate that inhibition of oxidative metabolism is probably not the primary site of the deleterious effects of nitric oxide and derivatives during early post-ischemic reperfusion.
Helps
Stephen C
SC
Department of Medical Biochemistry, Centre for Neuroscience, School of Medicine, Flinders University, GPO Box 2100, Adelaide, SA 5001, Australia.
Sims
Neil R
NR
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D007191:Indazoles / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000517:prevention & control / Q000601:surgery; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D007191:Indazoles; D010725:Phosphocreatine; D019344:Lactic Acid; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D005947:Glucose; C080122:7-nitroindazole