Probucol Improves Endothelial-Dependent Relaxation and Decreases Vascular Superoxide Production in Cholesterol-Fed Rabbits

doi:10.1016/S0002-9629(15)40320-9

The American Journal of the Medical Sciences

Volume 315, Issue 4, April 1998, Pages 242-247

https://doi.org/10.1016/S0002-9629(15)40320-9 Get rights and content

ABSTRACT

Recent data indicate that hypercholesterolemia increases endothelial superoxide anion (. O2-) production, and that this diminishes the bioactivity of nitric oxide produced in the endothelium. Probucol, a drug commonly employed for treatment of hypercholesterolemia, has antioxidant properties and inhibits oxidation of low density lipopro-teins in vitro. We tested the hypothesis that probucol would decrease vascular .O2-production and improve endothelium-dependent relaxations in cholesterol-fed rabbits. Rabbits were divided into four groups: 1) a control group fed a standard diet; 2) a probucol group fed a standard diet containing 0.3% probucol; 3) a hypercholesterolemic group fed a diet containing 0.5% cholesterol; 4) a hypercholesterolemia-probucol group fed a diet containing0.5% cholesterol and 0.3% probucol. The cholesterolrich diet markedly increased plasma total cholesterol level and lipid peroxidation in the plasma, as reflected by thiobarbituric acid-reactive substances (TBARS). This concentration of probucol did not lower plasma cholesterol, but markedly reduced TBARS in the plasma of cholesterol-fed rabbits. Aortic segments from cholesterol-fed rabbits produced 1.8-fold more .O2 -(assessed by lucigenin-enhanced chemiluminescence) and decreased en-dothelium-dependent vascular relaxations to acetylcholine compared to vessels from normal rabbits. In cholesterol-fed rabbits, probucol treatment normalized both.O2 -production and endothelium-dependent relaxations to acetylcholine. In control rabbits, probucol h~ no effect on either ofthese parameters.We co: clude that probucol treatment may prevel .O2-induced inactivation of endothelium-d rived nitric oxide and reduce vascular oxidal stress via reducing the level of .O2-.

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Original ArticlesProbucol Improves Endothelial-Dependent Relaxation and Decreases Vascular Superoxide Production in Cholesterol-Fed Rabbits

ABSTRACT

Eur J Pharmacol.

Biochem Biophys 20. Acta.

FEBS Lett.

J BioI Chem.

Cholesterol feeding impairs endothelial-dependent relaxation of rabbit aorta

Can J Physiol Pharmacol.

Atherosclerosis impairs endothelium-dependent vascular relaxation to acetylcholine and thrombin in primates

Circ Res.

Abnormal endothelium-dependent relaxation in patients with essential hypertension

N Engl J Med.

SM. Endothelium-dependent vasodilatation is attenuated in patients with heart failure

Circulation.

Chronic treatment with polyethylene- 17. glycolated superoxide dismutase partially restores endothelium-dependent vascular relaxations in cholesterol-fed rab* bits

Circ Res.

Hypercholesterol- 18. emia increases endothelial superoxide anion production

J Clin Invest.

Hypertension and the pathogenesis of atherosclerosis: oxidative stress and the mediation of arterial 19. inflammatory response: a new perspective

Hypertension.

Probucol inhibits oxidative modification of low 21. density lipoprotein

J Clin Invest.

Probucol prevents the progression of atherosclerosis in Watanabe heritable hyperlipidemic rab- 22. bit, an animal model for familial hypercholesterolemia

Proc Natl Acad Sci USA.

Original Articles
Probucol Improves Endothelial-Dependent Relaxation and Decreases Vascular Superoxide Production in Cholesterol-Fed Rabbits