Arginine NO-dependent and NO-independent effects on hemodynamics

L-arginine administration decreases mean arterial blood pressure (MABP), presumably by excess nitric oxide (NO) synthesis. However, some reports indicate that D-arginine, not a substrate of NO synthase (NOS), also induces hypotension. To clarify this phenomenon, the hemodynamic effects of L- and D-arginine and their modification by NOS inhibition with L-nitroarginine methyl ester (L-NAME) were assessed. MABP, cardiac output, stroke volume, heart rate and systemic vascular resistance were recorded in Sprague-Dawley rats under urethane or ketamine/diazepam anesthesia, with or without blockade of NO synthesis by L-NAME. Both stereoisomers of arginine induced a dose-related drop in MABP of similar magnitude and time course, but recovery from hypotension was slower in L-arginine than in D-arginine. The hypotension induced by both stereoisomers was due to a decrease in systemic vascular resistance (SVR) with increase in cardiac output (CO) and stroke volume (SV). Administration of L-NAME induced a pronounced increase in MABP and SVR, with decreases in CO and heart rate (HR). Infusion of L-arginine after L-NAME significantly decreased MABP and SVR at the highest dose while D-arginine failed to do so. After L-NAME, MABP was significantly lower under L-arginine than under D-arginine at all doses. These experiments suggest a dual mechanism in the hypotensive effect of L-arginine: a NO independent action on vascular resistance shared with D-arginine, and a NO dependent mechanism that becomes evident in the presence of NOS inhibition with L-NAME. Cardiac effects of NO do not appear to play a role in Larginine hypotensionFil: Guridi, Jorge. Universidad Nacional de Rosario. Facultad de Ciencias Médicas; ArgentinaFil: Borgatello, Conrado. Universidad Nacional de Rosario; ArgentinaFil: Scremin, Oscar Umberto. Universidad Nacional de Rosario; Argentina. Greater Los Angeles Healthcare System. Los Angeles; Estados Unidos. David Geffen School of Medicine at UCLA; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin