Original Contributions 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 JV-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 iV-nitro-D-arginine had no effect. L-Arginine reversed the pressor response. yV-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 JV-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. (Hypertension 1993;21:3-8)