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

Mügge A, Elwell JH, Peterson TE, Hofmeyer TG, Heistad DD, Harrison DG
Circ Res. 1991 69 (5): 1293-300

PMID: 1934359 · DOI:10.1161/01.res.69.5.1293

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.

MeSH Terms (14)

Acetylcholine Animals Blood Vessels Calcimycin Cholesterol Diet Endothelium, Vascular Female Male Polyethylene Glycols Rabbits Superoxide Dismutase Time Factors Vasodilation

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