Irbesartan, an angiotensin type 1 receptor inhibitor, regulates the vascular oxidative coronary artery disease state in patients with coronary arterydisease

OBJECTIVES The aim of this study was to determine the effect of angiotensin II type I (AT(1)) receptor antagonists on pro-oxidant species observed in the pathogenesis of atherosclerosis. Parameters such as low-density lipopro tein (LDL) susceptibility, monocyte binding capacity, superoxide generation and lipid peroxidation were examined in the presence of the AT, receptor a ntagonist irbesartan. BACKGROUND Low-density lipoprotein oxidation is a key component in the proc ess of atherogenesis. This modification may involve various mechanisms, inc luding changes in nitric oxide levels and superoxide levels. Additionally, compounds that suppress these mechanisms may retard or inhibit the pathogen esis of atherosclerosis. METHODS Forty-seven patients with documented coronary artery disease were t reated with irbesartan for a 12-week period. Patients were randomized to re ceive irbesartan or placebo. Lipid peroxidation, superoxide levels, monocyt e binding and LDL oxidation were measured at 0, 4 and 12 weeks. Findings we re statistically, evaluated by, two-way repeated measures, analysis of vari ance with p < 0.05 being significant. RESULTS Treatment with irbesartan significantly decreased the pro-oxidative environment seen in our study population. Lag time for LDL oxidation incre ased 32% at 12 weeks, suggesting an increased resistance of LDL modificatio n in the serum. Thiobarbituric acid reactive substances activity indicated that lipid peroxidation decreased by 36% in comparison to placebo. In addit ion, superoxide levels and monocyte-binding capacity were also significantl y reduced in coronary artery disease patients receiving irbesartan. CONCLUSIONS Our results indicate that irbesartan may suppress the atheroscl erotic process by inhibiting the intravascular oxidative state and the prod uction of reactive oxygen species, compounds that may cause damage to the v asculature. (C) 2001 by the American College of Cardiology.