Desmethyl tirilazad reduces brain nitric oxide synthase activity and cyclic guanosine monophosphate during cerebral global transient ischemia in rats.
Experiments were conducted to evaluate the effects of desmethyl tirilazad (10 mg/kg, i.p.), a 21-aminosteroid, on constitutive nitric oxide synthase (cNOS) activity and cyclic guanosine monophosphate (cGMP) levels in brain homogenates of rats subjected to cerebral global transient ischemia induced by bilateral clamping of the carotids for 30 minutes and reduction of arterial pressure (to 50-60 mmHg) by intravenous infusion of 1.5 ml of a solution of trimethaphan (5 mg/ml). Our results show that ischemia induces a rise in cNOS activity (from 62.0 +/- 6.1 to 133.3 +/- 13.3 pmol/min/mg protein) and cGMP levels (from 459.3 +/- 49.6 to 1074.1 +/- 132.1 fmol/mg protein). Pretreatment with desmethyl tirilazad abolishes these increases. These results are in agreement with the neuroprotective efficacy of desmethyl tirilazad in cerebral ischemia.
Fernández
M P
MP
Department of Pharmacology, School of Medicine, University of Santiago de Compostela, Spain.
Belmonte
A
A
Meizoso
M J
MJ
García-Novio
M
M
García-Iglesias
E
E
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002545:Brain Ischemia / Q000201:enzymology* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology; D006152:Cyclic GMP / Q000037:antagonists & inhibitors*; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011281:Pregnatrienes / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014294:Trimethaphan / Q000494:pharmacology
D011281:Pregnatrienes; C074965:U 74389F; D014294:Trimethaphan; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP