Probucol improves endothelial-dependent relaxation and decreases vascular superoxide production in cholesterol-fed rabbits

Nobutaka Inoue, Yuichi Ohara, Tohru Fukai, David G. Harrison, Ken'ichi Nishida

Research output: Contribution to journalArticle

41 Citations (Scopus)

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 arid inhibits oxidation of low density lipoproteins 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 containing 0.5% cholesterol and 0.3% probucol. The cholesterol-rich 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 endothelium-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 had no effect on either of these parameters. We conclude that probucol treatment may prevent ·O2 -induced inactivation of endothelium-derived nitric oxide and reduce vascular oxidant stress via reducing the level of ·O2 -.

Original languageEnglish (US)
Pages (from-to)242-247
Number of pages6
JournalAmerican Journal of the Medical Sciences
Volume315
Issue number4
DOIs
StatePublished - Jan 1 1998
Externally publishedYes

Fingerprint

Probucol
Superoxides
Blood Vessels
Cholesterol
Rabbits
Diet
Hypercholesterolemia
Endothelium
Thiobarbituric Acid Reactive Substances
Acetylcholine
Nitric Oxide
Luminescence
LDL Lipoproteins
Oxidants
Vasodilation
Lipid Peroxidation
Antioxidants

Keywords

  • Endothelial-dependent relaxation
  • Hypercholesterolemia
  • Probucol
  • Superoxide anion

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Probucol improves endothelial-dependent relaxation and decreases vascular superoxide production in cholesterol-fed rabbits. / Inoue, Nobutaka; Ohara, Yuichi; Fukai, Tohru; Harrison, David G.; Nishida, Ken'ichi.

In: American Journal of the Medical Sciences, Vol. 315, No. 4, 01.01.1998, p. 242-247.

Research output: Contribution to journalArticle

Inoue, Nobutaka ; Ohara, Yuichi ; Fukai, Tohru ; Harrison, David G. ; Nishida, Ken'ichi. / Probucol improves endothelial-dependent relaxation and decreases vascular superoxide production in cholesterol-fed rabbits. In: American Journal of the Medical Sciences. 1998 ; Vol. 315, No. 4. pp. 242-247.
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