Role of superoxide anion and endothelium in vasoconstrictor action of prostaglandin endoperoxide.
The vasoconstrictor actions of prostaglandin (PG) endoperoxide, PGH2, were examined in isolated rabbit aortic rings suspended for measurement of isometric tension. In aortic rings with an intact endothelium, PGH2 caused concentration-dependent contractions which were blocked by SQ 29548 (a PGH2-thromboxane A2 receptor blocker) or superoxide dismutase (a superoxide anion scavenger) but not by carbethoxyhexyl imidazole (a thromboxane A2 synthase inhibitor) or catalase (a hydrogen peroxide scavenger). In contrast U 46619, a thromboxane A2 mimic, caused contractions, which were blocked by SQ 29548 but not by superoxide dismutase. PGH2 caused significantly greater contractions in aortic rings without endothelium or in those with intact endothelium treated with NG-nitro-L-arginine, a nitric oxide inhibitor; these contractions were inhibited by SQ 29548 but not by superoxide dismutase. In aortic rings with endothelium contracted with phenylephrine, a subthreshold concentration of PGH2, but not U 46619, impaired relaxations to acetylcholine; the inhibition was prevented by treatment with SQ 29548 or superoxide dismutase, indicating that the abnormality of endothelial cell function was specific for PGH2. These observations indicate that PGH2 causes contractions and inhibits endothelium-dependent relaxation by a mechanism involving formation of superoxide anion, which interacts with endothelium-derived nitric oxide.
Tesfamariam
B
B
Robert Dawson Evans Department of Clinical Research, Boston University School of Medicine, Massachusetts 02118.
Cohen
R A
RA
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000838:Anions / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D011449:Prostaglandin Endoperoxides / Q000494:pharmacology*; D011817:Rabbits; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation
D000838:Anions; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011449:Prostaglandin Endoperoxides; D013481:Superoxides; D013928:Thromboxane A2; C045749:SQ 29548; D013482:Superoxide Dismutase; D000109:Acetylcholine