title: Arginine NO-dependent and NO-independent effects on hemodynamics.
abstract: 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.
authors: Departamento de Ciencias Fisiologicas, Facultad de Ciencias Medicas, Universidad Nacional de Rosario, Argentina; PROFISIO, Universidad Nacional de Rosario, Argentina.
authors: Jorge
authors: J
authors: Guridi
authors: PROFISIO, Universidad Nacional de Rosario, Argentina.
authors: Conrado
authors: C
authors: Borgatello
authors: PROFISIO, Universidad Nacional de Rosario, Argentina; VA Greater Los Angeles Healthcare System, 11301 Wilshire Boulevard, Los Angeles, CA 90073, USA; Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Consejo Nacional de Investigaciones Cientificas y Tecnicas, Argentina. Electronic address: oscremin@ucla.edu.
authors: Oscar U
authors: OU
authors: Scremin
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester
keywords: Arterial blood pressure; Cardiac output; Nitric oxide synthase; Systemic vascular resistance; l-NAME