CENTRAL INHIBITION OF NITRIC-OXIDE SYNTHESIS INCREASES BLOOD-PRESSUREAND HEART-RATE IN ANESTHETIZED RATS

In the present study we evaluated the cardiovascular responses to inhi bition of endogenous nitric oxide (NO)formation in the brain with intr acerebroventricular (i.c.v.) administration of N-omega-nitro-L-arginin e methyl ester (L-NAME), a specific inhibitor of NO synthase. L-NAME ( 30 mu g and 300 mu g i.c.v.) induced a dose-dependent increase in mean arterial pressure and heart rate in anesthetized normotensive rats, w hile its enantiomer D-NAME (300 mu g i.c.v.) increased blood pressure only slightly and transiently. The presser response to L-NAME was part ially attenuated by i.c.v. administration of NO precursor L-arginine ( 300 mu g), whereas D-arginine, the stereoisomer which cannot serve as a precursor for the biosynthesis of NO, was ineffective. Inhibition of beta(1)-adrenoceptors by pretreatment with atenolol (2.5 mg/kg i.v.) reduced the presser and tachycardic effect of subsequently administere d L-NAME, whereas muscarinic receptor antagonist methylatropine (2 mg/ kg i.v.) did not affect the cardiovascular effects of L-NAME. These fi ndings imply that the presser response to i.c.v. L-NAME results from w ithdrawal of the inhibitory effect of endogenous NO on a central press or mechanism which acts by increasing sympathetic outflow.