Effects of nitric oxide synthase inhibition on sympathetically-mediated tachycardia

The aim of the present study was to determine whether inhibition of nitric oxide (NO) synthesis directly alters the tachycardia produced by sympatheti cally-derived norepinephrine. The NO synthase inhibitor, N-G-nitro-L-argini ne methyl ester (L-NAME; 50 mu mol/kg, iv), produced st marked rise in mean arterial blood pressure. This presser response was associated with a fall in heart rate which involved the withdrawal of cardiac sympathetic nerve ac tivity. The NO-donor, sodium nitroprusside (5 mu g/kg, iv), produced a pron ounced fall in mean arterial blood pressure but only a minor increase in he art rate. The beta-adrenoceptor agonist, isoproterenol (0.5 mu mol/kg, iv), and the membrane-permeable cAMP analogue, 8-(4-chlorophenylthiol)-cAMP (10 mu mol/kg, iv), produced falls in mean arterial blood pressure and pronoun ced increases in heart rate. The indirectly acting sympathomimetic agent, t yramine (0.5 mg/kg, iv), produced a presser response and a tachycardia The effects of sodium nitroprusside, tyramine, isoproterenol and 8-(4-chlorophe nylthiol)cAMP on mean arterial blood pressure were not markedly affected by L-NAME. However, the tachycardia produced by these agents was considerably exaggerated in the presence of this NO synthesis inhibitor. These findings suggest that L-NAME potentiates the tachycardia produced by sympatheticall y-derived norepinephrine. The increased responsiveness to norepinephrine ma y involve (i) a rapid up-regulation of cardiac beta(1)-adrenoceptors and cA MP signaling in cardiac pacemaker cells due to the loss of the inhibitory i nfluence of cardiac NO, and (ii) the up-regulation of beta(1)-adrenoceptor- mediated signal transduction processes in response to the L-NAME-induced wi thdrawal of cardiac sympathetic nerve activity. (C) 1999 Elsevier Science B .V. All rights reserved.