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Inhibition of Coronary Artery Superoxide Dismutase Attenuates Endothelium-Dependent and -Independent Nitrovasodilator Relaxation
Circulation Research (1991)
  • Hatim A. Omar
  • P. D. Cherry
  • M. P. Mortelliti
  • T. Burke-Wolin
  • M. S. Wolin
Abstract
Isolated bovine coronary arteries were treated with 10 mM diethyldithiocarbamate (DETCA) for 30 minutes to deplete the cytosolic ZnCu form of superoxide dismutase (SOD). This treatment completely inhibited the endothelium- and cGMP-dependent relaxation to acetylcholine (mediated via the endothelium-derived relaxing factor, which is thought to be nitric oxide) without significantly inhibiting endothelium-dependent relaxation to arachidonic acid (mediated by prostaglandins). DETCA treatment of endothelial cells cultured from the coronary arteries inhibited bradykinin-elicited release of endothelium-derived relaxing factor, which was detected by bioassay on an isolated rabbit aorta in the presence of extracellular SOD. DETCA also inhibited cGMP-associated relaxations to nitric oxide and to vasodilators thought to function via the generation of this mediator (nitroglycerin and nitroprusside), but cAMP-associated relaxations to isoproterenol and papaverine were not altered. The inhibitory effects of DETCA against the relaxation to nitroprusside and nitroglycerin were attenuated by severe hypoxia. DETCA treatment of isolated coronary arterial smooth muscle or cultured endothelial cells produced an increase of chemiluminescence elicited in the presence of lucigenin, a detector of superoxide anion generation. The addition of SOD markedly attenuated the effects of DETCA treatment on arterial relaxation and chemiluminescence. Therefore, control of cellular superoxide anion levels by endogenous SOD appears needed for the release of endothelium-derived relaxing factor and relaxation of vascular smooth muscle to nitrovasodilators mediated via cGMP in the bovine coronary artery, but SOD is not critical for other endothelium-dependent or cAMP-associated relaxant mechanisms.
Keywords
  • Coronary artery superoxide,
  • nitrovasodilator relaxation
Disciplines
Publication Date
1991
Citation Information
Hatim A. Omar, P. D. Cherry, M. P. Mortelliti, T. Burke-Wolin, et al.. "Inhibition of Coronary Artery Superoxide Dismutase Attenuates Endothelium-Dependent and -Independent Nitrovasodilator Relaxation" Circulation Research Vol. 69 (1991)
Available at: http://works.bepress.com/hatim_omar/65/