1. Effect of losartan in aging-related endothelial impairment
- Author
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Rajagopalan, Sanjay, Brook, Robert, Mehta, Rajendra H., Supiano, Mark, and Pitt, Bertram
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PHYSIOLOGICAL aspects of aging , *ENDOTHELIUM diseases , *AGING , *ANTIGENS , *BLOOD pressure , *CELL adhesion molecules , *CLINICAL trials , *COMPARATIVE studies , *CROSSOVER trials , *ENDOTHELIUM , *INFLAMMATORY mediators , *LONGITUDINAL method , *VASCULAR resistance , *RESEARCH methodology , *MEDICAL cooperation , *RESEARCH , *EVALUATION research , *BRACHIAL artery , *RANDOMIZED controlled trials , *BLIND experiment , *LOSARTAN , *PHARMACODYNAMICS - Abstract
Aging is associated with progressive deterioration in endothelial function. We hypothesized that losartan may represent a useful therapeutic strategy to ameliorate endothelial function in aged subjects. Eighteen healthy older subjects (mean age 75 ± 3 years) were prospectively randomized in a double-blind, crossover fashion to receive either losartan 50 mg/day or placebo for 6 weeks. Subjects were switched to the opposite arm after a 2- week washout period. Flow-mediated dilation (FMD) in the brachial artery and plasma levels of vascular cell adhesion molecule-1, intercellular adhesion molecule (ICAM), moncocyte chemoattractant 1 protein, and E-selectin were measured in both arms at the beginning and end of the 6-week period. Losartan resulted in a 6-mm Hg decrease in systolic blood pressure (from 130 ± 12 to 124 ± 13 mm Hg), which was no different from placebo (132 ± 12 to 127 ± 13 mm Hg). FMD increased from 3.1 ± 0.6% to 3.9 ± 0.6% after losartan, and decreased from 3.3 ± 0.3% to 2.4 ± 0.6% after placebo (p = NS for both). In contrast, losartan reduced circulating concentrations of vascular cell adhesion molecule 1 (750 ± 73 to 572 ± 39), ICAM (405 ± 26 to 196 ± 10), and moncocyte chemoattractant 1 protein (560 ± 56 to 423 ± 35) (p <0.01 for all by analysis of variance), but not E-selectin. On univariate analyses, the strongest predictor of baseline endothelial function and change in FMD with losartan was low-density lipoprotein. There was a negative correlation between baseline endothelial function and change in FMD in response to losartan (r2 = −0.75, p = 0.0003). Baseline ICAM levels alone significantly correlated with low-density lipoprotein cholesterol (r2 = 0.54, p = 0.02) and weakly correlated with total cholesterol (r2 = 0.47, p = 0.05). Thus, administration of losartan for a duration of 6 weeks has favorable effects on inflammatory markers in healthy older subjects, but does not alter peripheral conduit endothelial function. [Copyright &y& Elsevier]
- Published
- 2002
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