NG-methylarginine, and inhibitor of endothelium-derived nitric oxide synthesis, is a potent pressor agent in the guinea pig: Does nitric oxide regulate blood pressure in vivo?

Nitric oxide is a major endothelium-derived vascular smooth muscle relaxing factor; its synthesis from L-arginine is selectively inhibited by L-NG-methylarginine. To assess whether basal nitric oxide release contributes to blood pressure regulation in vivo, we have investigated the cardiovascular effects of L-NG-methylarginine in the anesthetized guinea pig. L-NG-methylarginine (0.1-10 mg/kg, i.v. bolus) elicited a sustained, dose-dependent, increase in arterial pressure and a moderate bradycardia. L-arginine (30 mg/kg i.v.) prevented or reversed the pressor effect of L-NG-methylarginine, while atropine (2 mg/kg) abolished the associated bradycardia. In contrast, L-arginine did not attenuate the pressor effect of norepinephrine or angiotensin. Our findings suggest that basal nitric oxide production is sufficient to modulate peripheral vascular resistance; hence nitric oxide may play a role in arterial pressure homeostasis.