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We studied the differences between isosorbide dinitrate (ISDN) and L-arginine (L-Arg), the precursor of nitric oxide, regarding autonomic nervous function by assessing changes in heart rate variability and blood levels of various vasoactive substances. Healthy volunteers received infused L-arginine (L-Arg group) or isosorbide dinitrate (ISDN group). ECGs were monitored and analyzed. Blood levels of catecholamines, endothelin, renin activity, angiotensin, human atrial natriuretic peptide, aldosterone, arginine, and citrulline were examined. Time-domain analyses of heart rate variability showed no significant changes in occurrence of R-R variability or coefficient of R-R variability, indicators of parasympathetic activity, after administration of ISDN. By contrast, both measures showed significantly more variation following administration of L-Arg. Frequency-domain analyses showed that high frequency power, an indicator of parasympathetic activity, was significantly elevated in the L-Arg group, whereas there was no significant change in the ISDN group. The blood levels of the measured vasoactive substances in L-Arg and ISDN groups were significantly different. The differences in autonomic nervous function and various kinds of vasoactive substances between the L-Arg and ISDN groups suggest that L-Arg had other actions on humoral factors in addition to vasodilation. Thus, arginine/nitric oxide may act as a neurotransmitter, altering parasympathetic nervous tension.

Effects of Intravenous Administration of L-arginine on Autonomic Nervous Acffvities. Analysis of Heart Rate Variability.