Effect of losartan in aging-related endothelial impairment.
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 (r(2) = -0.75, p = 0.0003). Baseline ICAM levels alone significantly correlated with low-density lipoprotein cholesterol (r(2) = 0.54, p = 0.02) and weakly correlated with total cholesterol (r(2) = 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.
Rajagopalan
Sanjay
S
Department of Internal Medicine, Divisions of Cardiology, University of Michigan School of Medicine, Ann Arbor, Michigan 48109-0273, USA. srajagop@umich.edu
Brook
Robert
R
Mehta
Rajendra H
RH
Supiano
Mark
M
Pitt
Bertram
B
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D001916:Brachial Artery / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000097:blood; D018932:Chemokine CCL2 / Q000097:blood; D015331:Cohort Studies; D018592:Cross-Over Studies; D004311:Double-Blind Method; D019040:E-Selectin / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D006801:Humans; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects
D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D019040:E-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D019808:Losartan