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

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 lipoprotein (LDL) susceptibility, monocyte binding capacity, superoxide generation and lipid peroxidation were examined in the presence of the AT, receptor antagonist irbesartan. BACKGROUND Low-density lipoprotein oxidation is a key component in the process of atherogenesis. This modification may involve various mechanisms, including changes in nitric oxide levels and superoxide levels. Additionally, compounds that suppress these mechanisms may retard or inhibit the pathogenesis of atherosclerosis. METHODS Forty-seven patients with documented coronary artery disease were treated with irbesartan for a 12-week period. Patients were randomized to receive irbesartan or placebo. Lipid peroxidation, superoxide levels, monocyte binding and LDL oxidation were measured at 0, 4 and 12 weeks. Findings were statistically, evaluated by, two-way repeated measures, analysis of variance 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 increased 32% at 12 weeks, suggesting an increased resistance of LDL modification in the serum. Thiobarbituric acid reactive substances activity indicated that lipid peroxidation decreased by 36% in comparison to placebo. In addition, superoxide levels and monocyte-binding capacity were also significantly reduced in coronary artery disease patients receiving irbesartan. CONCLUSIONS Our results indicate that irbesartan may suppress the atherosclerotic process by inhibiting the intravascular oxidative state and the production of reactive oxygen species, compounds that may cause damage to the vasculature. (C) 2001 by the American College of Cardiology.