Circulation Research, Vol 69, 1293-1300, Copyright © 1991 by American Heart Association

ARTICLES

Chronic treatment with polyethylene-glycolated superoxide dismutase partially restores endothelium-dependent vascular relaxations in cholesterol-fed rabbits

A Mugge, JH Elwell, TE Peterson, TG Hofmeyer, DD Heistad and DG Harrison
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City.

The endothelium-derived relaxing factor is rapidly inactivated by superoxide radicals, and atherosclerotic vessels generate excess radical species. We tested the hypothesis that an imbalance between intrinsic superoxide dismutase (SOD) activity and the generation of superoxide radicals in atherosclerotic arteries may result in augmented inactivation of endothelium-derived relaxing factor. Vascular SOD was increased in normal and cholesterol-fed (1% cholesterol for 4 months) rabbits approximately twofold by treatment with polyethylene-glycolated SOD (PEG-SOD; 41,000 units/kg/day i.m.) for 1 week. Aortic rings from these animals and nontreated control and atherosclerotic rabbits subsequently were studied in organ chambers. Endothelium-dependent relaxations to acetylcholine and the calcium ionophore A23187 were improved by PEG-SOD in atherosclerotic but not in normal rabbits. PEG- SOD pretreatment did not alter endothelium-independent relaxations to nitroprusside. Thus, treatment with PEG-SOD can partially restore impaired endothelium-dependent relaxation of atherosclerotic arteries. We conclude that generation of oxygen-derived radicals likely contributes to endothelial dysfunction of atherosclerotic arteries.

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				F. Diet, R. E. Pratt, G. J. Berry, N. Momose, G. H. Gibbons, and V. J. Dzau Increased Accumulation of Tissue ACE in Human Atherosclerotic Coronary Artery Disease Circulation, December 1, 1996; 94(11): 2756 - 2767. [Abstract] [Full Text]

				N. Inoue, S. Ramasamy, T. Fukai, R. M. Nerem, and D. G. Harrison Shear Stress Modulates Expression of Cu/Zn Superoxide Dismutase in Human Aortic Endothelial Cells Circ. Res., July 1, 1996; 79(1): 32 - 37. [Abstract] [Full Text]

				S. L. Pfister and W. B. Campbell Reduced Pulmonary Artery Vasoconstriction to Methacholine in Cholesterol-Fed Rabbits Hypertension, March 1, 1996; 27(3): 804 - 810. [Abstract] [Full Text]

				J. Galle, J. Bengen, P. Schollmeyer, and C. Wanner Impairment of Endothelium-Dependent Dilation in Rabbit Renal Arteries by Oxidized Lipoprotein(a) : Role of Oxygen-Derived Radicals Circulation, September 15, 1995; 92(6): 1582 - 1589. [Abstract] [Full Text]

				A. M. Zeiher, V. Schachinger, and J. Minners Long-term Cigarette Smoking Impairs Endothelium-Dependent Coronary Arterial Vasodilator Function Circulation, September 1, 1995; 92(5): 1094 - 1100. [Abstract] [Full Text]

				Y. Ohara, T. E. Peterson, H. S. Sayegh, R. R. Subramanian, J. N. Wilcox, and D. G. Harrison Dietary Correction of Hypercholesterolemia in the Rabbit Normalizes Endothelial Superoxide Anion Production Circulation, August 15, 1995; 92(4): 898 - 903. [Abstract] [Full Text]

				K. P. Moore, V. Darley-Usmar, J. Morrow, and L. J. Roberts II Formation of F2-Isoprostanes During Oxidation of Human Low-Density Lipoprotein and Plasma by Peroxynitrite Circ. Res., August 1, 1995; 77(2): 335 - 341. [Abstract] [Full Text]

				C. B. Treasure, J. L. Klein, W. S. Weintraub, J. D. Talley, M. E. Stillabower, A. S. Kosinski, J. Zhang, S. J. Boccuzzi, J. C. Cedarholm, and R. W. Alexander Beneficial Effects of Cholesterol-Lowering Therapy on the Coronary Endothelium in Patients with Coronary Artery Disease N. Engl. J. Med., February 23, 1995; 332(8): 481 - 487. [Abstract] [Full Text] [PDF]

				R. W. Alexander Hypertension and the Pathogenesis of Atherosclerosis : Oxidative Stress and the Mediation of Arterial Inflammatory Response: A New Perspective Hypertension, February 1, 1995; 25(2): 155 - 161. [Abstract] [Full Text]