Nitric oxide inactivates endothelium-derived contracting factor in the rat aorta.
Acetylcholine evokes the simultaneous release of endothelium-derived relaxing and contracting factors in aortas from spontaneously hypertensive rats. Only relaxing factors are released in aortas from normotensive controls. Experiments were designed to determine whether inhibitors of endothelium-dependent relaxations modify endothelium-dependent contractions. Rings of thoracic aortas of normotensive and spontaneously hypertensive rats, with and without endothelium, were suspended in organ chambers for isometric tension recording. Oxyhemoglobin (a scavenger of endothelium-derived relaxing factor) and NG-monomethyl L-arginine (an inhibitor of nitric oxide formation) augmented the contractions to acetylcholine. Methylene blue (an inhibitor of soluble guanylate cyclase) and superoxide dismutase (a scavenger of superoxide anions) did not modify these contractions. The contractions in the presence of oxyhemoglobin or NG-monomethyl L-arginine, like those in untreated rings, were endothelium-dependent; they only occurred in aortas from spontaneously hypertensive rats and were abolished by indomethacin. The contractions to acetylcholine in the presence of oxyhemoglobin were not affected by superoxide dismutase or deferoxamine. These data suggest that endothelium-derived relaxing factor inhibits endothelium-dependent contractions to acetylcholine in the spontaneously hypertensive rat aorta, probably by chemical inactivation of the endothelium-derived contracting factor rather than by stimulation of guanylate cyclase or scavenging of oxygen-derived free radicals.
Auch-Schwelk
W
W
Mayo Clinic, Mayo Foundation, Department of Physiology and Biophysics, Rochester, Minn.
Katusić
Z S
ZS
Vanhoutte
P M
PM
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects*; D016166:Free Radical Scavengers; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D010108:Oxyhemoglobins / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019323:omega-N-Methylarginine
D016166:Free Radical Scavengers; D010108:Oxyhemoglobins; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D013482:Superoxide Dismutase; D000109:Acetylcholine; D010100:Oxygen; D008751:Methylene Blue