Arginine NO-dependent and NO-independent effects on hemodynamics

作者：Guridi Jorge; Borgatello Conrado; Scremin Oscar U^*

来源：European Journal of Pharmacology, 2014, 729: 138-143.

DOI：10.1016/j.ejphar.2014.01.070

• L-NAME
• Nitric oxide synthase
• Arterial blood pressure
• Cardiac output
• Systemic vascular resistance

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 close-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 clue 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 I-NAME significantly decreased MABP and SVR at the highest dose while D-arginine failed to do so. After I-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. Published by Elsevier B.V.

• 出版日期2014-4-15