Author + information
- Received January 23, 2001
- Revision received July 13, 2001
- Accepted August 9, 2001
- Published online November 15, 2001.
- Bobby V Khan, MD, PhD*,*,†,‡ (, )
- Sushant Navalkar, MD*,†,‡,
- Qamar A Khan, MD, FACC*,‡,
- Syed T Rahman, MD*,‡ and
- Sampath Parthasarathy, PhD†,‡
- ↵*Reprint requests and correspondence: Dr. Bobby V. Khan, Emory University School of Medicine, Division of Cardiology, 69 Butler Street SE, #C233, Atlanta, Georgia 30303 USA
The aim of this study was to determine the effect of angiotensin II type 1 (AT1) 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 AT1receptor antagonist irbesartan.
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.
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.
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.
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.
☆ Financial support for this study was through a grant from the NIH/NHLBI Division (K08/HL03137 to B.V.K.).
- Received January 23, 2001.
- Revision received July 13, 2001.
- Accepted August 9, 2001.
- American College of Cardiology