Similarities between effects of superoxide-mediated endothelium-derived relaxing factor and cromakalim.
A stable endothelium-derived relaxing factor has been reported to be generated on exposure of endothelial cells to the superoxide anion. In this study, we first evaluated the effects of the relaxing factor and cromakalim on mechanical tone and, second, assessed their consequences on the 86Rb efflux rate. On application of hypoxanthine-xanthine oxidase to a bath for generating superoxide anion, the precontracted rabbit mesenteric artery exhibited another transient increase in contraction, followed by sustained relaxation. This relaxation was lost in the K(+)-physiological salt solution (PSS) (greater than 35 mM) and was inhibited by glibenclamide (10 microM) but not by N-methyl-L-arginine or methylene blue. Hypoxanthine-xanthine oxidase application did not increase either basal or stimulated synthesis of guanosine 3',5'-cyclic monophosphate. In the presence of 2 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid and 10 mM MgCl2, the relaxing factor caused a significant increase in 86Rb efflux from the aortic and mesenteric arterial segments, as did the cromakalim. The increased 86Rb efflux, either by the relaxing factor or by cromakalim, was wholly inhibited by glibenclamide. These results suggest that superoxide-mediated endogenous relaxing factor may have a similar mechanism of action to cromakalim in vasodilatation.
Kim
C D
CD
Department of Pharmacology, College of Medicine, Pusan National University, Korea.
Lee
W S
WS
Rhim
B Y
BY
Hong
K W
KW
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001578:Benzopyrans / Q000494:pharmacology*; D019806:Cromakalim; D006152:Cyclic GMP / Q000378:metabolism; D005260:Female; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D011817:Rabbits; D012413:Rubidium / Q000378:metabolism; D013481:Superoxides / Q000494:pharmacology*; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000494:pharmacology
D001578:Benzopyrans; D007042:Hypoxanthines; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D013481:Superoxides; D019271:Hypoxanthine; D009569:Nitric Oxide; D014969:Xanthine Oxidase; D006152:Cyclic GMP; D012413:Rubidium