Neural mechanism of hypertension by nitric oxide synthase inhibitor in dogs.
This study aimed to determine the mechanism of hypertension associated with nitric oxide synthase inhibition. Intravenous injections of NG-nitro-L-arginine, a nitric oxide synthase inhibitor, produced a sustained increase in systemic blood pressure and a decrease in heart rate in anesthetized dogs, whereas NG-nitro-D-arginine had no effect. L-Arginine reversed the pressor response. NG-Nitro-L-arginine-induced hypertension was markedly attenuated or abolished by treatment with hexamethonium; this inhibition was still observed when the blood pressure fall caused by the ganglionic blocking agent was compensated by continuous infusion of angiotensin II. In dogs treated with phentolamine in a dose sufficient to lower blood pressure to the level similar to that elicited by hexamethonium and to suppress the pressor response to norepinephrine, the hypertensive effect of NG-nitro-L-arginine was not attenuated. We conclude that hypertension caused by the nitric oxide synthase inhibitor is associated with an elimination of nitroxidergic neural function rather than an impairment of the basal release of nitric oxide from the endothelium.
Toda
N
N
Department of Pharmacology, Shiga University of Medical Sciences, Ohtsu, Japan.
Kitamura
Y
Y
Okamura
T
T
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D010646:Phentolamine / Q000494:pharmacology
D006584:Hexamethonium Compounds; D019335:Nitroarginine; D018738:Hexamethonium; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D010646:Phentolamine