L‐Arginine‐induced hypotension in the rat: evidence that NO synthesis is not involved

Abstract

L-Arginine is the biological precursor for nitric oxide (NO). NO is formed continuously in endothelial cells and maintains a certain degree of vasodilator tone under physiological conditions. Although the formation of NO is not primarily controlled by precursor availability, the extent to which extra supplementation with L-arginine may affect endothelial NO formation, and hence, vasodilator tone and systemic blood pressure, is not entirely clear. To address this issue, we infused L-arginine i.v. in anaesthetized normotensive rats pretreated with NG-nitro-L-arginine methyl ester (L-NAME, 50 or 200 mg-1) and in untreated controls, under continued recording of mean arterial pressure (MAP). In control animals L-arginine (25 or 100 mg kg-1 min-1) had no effect on systemic MAP (111 +/- 3 mm Hg), while L-arginine (200 mg kg-1 min-1) lowered MAP (to 70 +/- 6 mm Hg). D-Arginine (200 mg kg-1 min-1) also induced hypotension; during infusion of D-arginine MAP fell from 106 +/- 4 to 64 +/- 4 mm Hg. Pretreatment with L-NAME (50 and 200 mg kg-1) elevated MAP to 140 +/- 2 and 147 +/- 3 mm Hg, respectively, but failed to affect the hypotensive response to L-arginine; during infusion of L-arginine (200 mg kg-1 min-1) in rats pretreated with L-NAME (50 and 200 mg kg-1) MAP fell to 86 +/- 9 and 104 +/- 6 mm Hg, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)