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 l-arginine hypotension.