Role of endothelium-derived nitric oxide in the regulation of blood pressure.
The role of endothelium-derived nitric oxide in the regulation of blood pressure in the anesthetized rabbit was studied with N omega-monomethyl-L-arginine (L-NMMA), a specific inhibitor of its formation from L-arginine. L-NMMA (3-100 mg.kg-1), but not its D-enantiomer, induced a dose-dependent long-lasting (15-90 min) increase in mean systemic arterial blood pressure. L-NMMA (100 mg.kg-1) also inhibited significantly the hypotensive action of acetylcholine, without affecting that of glyceryl trinitrate. Both these actions of L-NMMA were reversed by L-arginine (300 mg.kg-1), but not by D-arginine (300 mg.kg-1), indomethacin (1 mg.kg-1), prazosin (0.3 mg.kg-1), or by vagotomy. The effects of L-NMMA in vivo were associated with a significant inhibition of the release of nitric oxide from perfused aortic segments ex vivo. This inhibition was reversed by infusing L-arginine through the aortic segments. These results indicate that nitric oxide formation from L-arginine by the vascular endothelium plays a role in the regulation of blood pressure and in the hypotensive actions of acetylcholine.
Rees
D D
DD
Wellcome Research Laboratories, Beckenham, Kent, United Kingdom.
Palmer
R M
RM
Moncada
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D005996:Nitroglycerin / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011817:Rabbits; D013237:Stereoisomerism; D014628:Vagotomy; D019323:omega-N-Methylarginine
D010656:Phenylephrine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D005996:Nitroglycerin; D000109:Acetylcholine; D011224:Prazosin; D007213:Indomethacin