The regressive effect of an angiotensin II receptor blocker on formed fatty streaks in monkeys fed a high-cholesterol diet

J Hypertens. 2005 Oct;23(10):1879-86. doi: 10.1097/01.hjh.0000182527.52063.32.

Abstract

Objectives: To clarify the regressive effect of an angiotensin II type 1 receptor blocker (ARB) on already formed fatty streaks, we investigated the effect of the administration of an ARB, olmesartan, on formed fatty streaks in monkeys fed a high-cholesterol diet.

Methods: After the monkeys were fed a high-cholesterol diet for 6 months, intimal hyperplasia was clearly observed on intravascular ultrasound. For the next 6 months, the high-cholesterol diet was continued, and olmesartan (3 mg/kg per day) or placebo was administered. A control group was fed a normal diet for 12 months.

Results: Olmesartan did not significantly affect blood pressure or plasma cholesterol levels throughout the experiment. After 6 months of treatment with olmesartan, intimal hyperplasia was significantly lower than before treatment. Acetylcholine-induced relaxation in isolated carotid arteries was significantly less in the high-cholesterol diet placebo-treated group compared to the normal diet group, whereas its response was improved by olmesartan. Serum levels of monocyte chemoattractant protein were significantly increased with a high cholesterol load, but they were significantly suppressed by olmesartan.

Conclusions: We have demonstrated for the first time that an ARB, olmesartan, was found to have a regressive effect on formed fatty streaks in monkeys.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Animals
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / enzymology
  • Aorta, Thoracic / pathology
  • Atherosclerosis / diagnostic imaging
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Carotid Arteries / drug effects
  • Carotid Arteries / physiology
  • Chemokine CCL2 / blood
  • Cholesterol / blood
  • Cholesterol, Dietary / administration & dosage*
  • Dose-Response Relationship, Drug
  • Hyperplasia
  • Imidazoles / therapeutic use
  • In Vitro Techniques
  • Lipids / biosynthesis
  • Macaca fascicularis
  • Male
  • Peptidyl-Dipeptidase A / blood
  • Peptidyl-Dipeptidase A / metabolism
  • Random Allocation
  • Renin / blood
  • Reproducibility of Results
  • Tetrazoles / therapeutic use
  • Time Factors
  • Tunica Intima / diagnostic imaging
  • Tunica Intima / drug effects*
  • Tunica Intima / pathology
  • Ultrasonography, Interventional / methods
  • Vasodilation / drug effects
  • Vasodilator Agents / pharmacology

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Chemokine CCL2
  • Cholesterol, Dietary
  • Imidazoles
  • Lipids
  • Tetrazoles
  • Vasodilator Agents
  • olmesartan
  • Cholesterol
  • Peptidyl-Dipeptidase A
  • Renin
  • Acetylcholine