Effects of intravenous arginine administration on cerebral circulation in the rat.

Abstract

The present study was designed to determine the effects of intravenous infusion of L-arginine (ARG), an endogenous precursor of nitric oxide (NO), on the cerebral circulation in the rat. Systemic arterial blood pressure (ABP) was continuously recorded, and local cerebral blood flow (LCBF) was measured by the iodo[14C]antipyrine method at a point of time as follows: In Saline group (n = 12); at 3 min after an intravenous injection of saline. In NG-monomethyl-L-arginine (L-NMMA) group (n = 7); at 3 min after an injection of L-NMMA (30 mg/kg/30 sec). In L-NMMA+L-ARG group (n = 7); at 3 min after an infusion of L-ARG free base (300 mg/kg/1 min) 3 min after prior injection of L-NMMA (30 mg/kg/30 sec). In L-ARG-1 group (n = 7); during an infusion of L-ARG free base (300 mg/kg/1 min). In L-ARG-2 group (n = 8); at 3 min after an administration of L-ARG free base (300 mg/kg/1 min). In D-ARG group (n = 5); at 3 min after an infusion of D-ARG free base (300 mg/kg/1 min). (1) The diffuse reduction in LCBF and increase in ABP induced by L-NMMA were almost completely reversed by excess L-ARG. (2) During the administration of L-ARG, a sustained decrease in ABP was observed, but LCBF revealed no significant change. (3) At 3 min after the infusion of L-ARG, LCBF was significantly decreased in several regions, while ABP recovered. (4) The infusion of D-ARG also induced a transient decrease in ABP, but did not alter LCBF. The effect of L-ARG on ABP may not be entirely due to an increase in substrate availability for NO synthase, since the D-enantiomer also had some vasodilatory property. Regarding the therapeutic application of L-ARG, further investigations on its actions should be performed under various conditions.