Modulation of the vasodepressor actions of acetylcholine, bradykinin, substance P and endothelin in the rat by a specific inhibitor of nitric oxide formation.
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 mumol 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 mumol 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 mumol 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.
Whittle
B J
BJ
Department of Pharmacology, Wellcome Research Laboratories, Kent.
Lopez-Belmonte
J
J
Rees
D D
DD
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology*; D016232:Endothelins; D011464:Epoprostenol / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D005996:Nitroglycerin / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D013237:Stereoisomerism; D013373:Substance P / Q000494:pharmacology*; D019323:omega-N-Methylarginine
D016232:Endothelins; D010455:Peptides; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D013373:Substance P; D001120:Arginine; D011464:Epoprostenol; D005996:Nitroglycerin; D000109:Acetylcholine; D001920:Bradykinin