Modulation of the vasodepressor actions of acetylcholine, bradykinin, substance P and endothelin in the rat by a specific inhibitor of nitric oxide formation

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Abstract
1 The effects of the specific inhibitor of nitric oxide (NO) formation, NG-monomethyl-L-arginine (L-NMMA), on resting systemic arterial blood pressure (BP) and on the actions of both endothelium-dependent and endothelium-independent vasodilators were investigated in the anaesthetized, normotensive rat. 2 Intravenous administration of L-NMMA (12.5–50 mg kg−1; 47–188 μmol kg−1) but not its enantiomer, D-NMMA, induced a dose-related increase in BP, which was reversed by the intravenous administration of L-arginine (150–600 μmol kg−1), but not D-arginine. 3 The vasodepressor responses to intravenous administration of the endothelium-dependent vasodilators, acetylcholine, bradykinin and substance P were significantly inhibited by L-NMMA (94 and 188 μmol kg−1 i.v.), but not by D-NMMA. 4 The inhibition by L-NMMA of these vasodepressor responses was reversed by administration of L-arginine, but not D-arginine. 5 Endothelin (ET-1) induced dose-related vasodepressor responses following bolus intravenous administration, which were significantly inhibited by L-NMMA but not by D-NMMA. This inhibition was reversed by administration of L-arginine. 6 The vasodepressor effects of the endothelium-independent vasodilators, glyceryl trinitrate or prostacyclin, were not significantly inhibited by L-NMMA. 7 These findings with L-NMMA suggest that resting blood pressure in the rat is modulated by endogenous NO biosynthesis and that endothelium-dependent vasodilators act through the formation of endogenous NO to exert their actions in vivo.