Effect of losartan in aging-related endothelial impairment.
Effect of losartan in aging-related endothelial impairment.
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氯沙坦对衰老相关内皮损伤的影响。
DOI：
10.1016/s0002-9149(01)02297-4
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Pitt,Bertram
中科院分区：
文献类型：
--
作者：
Rajagopalan,Sanjay;Brook,Robert;Mehta,RajendraH;Supiano,Mark;Pitt,Bertram
衰老与内皮功能的进行性恶化有关。我们假设氯沙坦可能是一种有效的治疗策略，以改善老年人的内皮功能。18名健康老年受试者（平均年龄75 ± 3岁）以双盲、交叉方式前瞻性随机接受氯沙坦50 mg/天或安慰剂治疗6周。受试者在2周洗脱期后转换至对侧治疗组。在6周的开始和结束时，测量两组肱动脉的流量介导的扩张（FMD）和血管细胞粘附分子-1、细胞间粘附分子（ICAM）、单核细胞趋化因子1蛋白和E-选择素的血浆水平。氯沙坦导致收缩压降低6 mm Hg（从130 ± 12 mm Hg降至124 ± 13 mm Hg），与安慰剂（132 ± 12 mm Hg降至127 ± 13 mm Hg）无差异。氯沙坦治疗后FMD从3.1 ± 0.6%增加至3.9 ± 0.6%，安慰剂治疗后FMD从3.3 ± 0.3%降低至2.4 ± 0.6%（两组p = NS）。相比之下，氯沙坦降低了血管细胞粘附分子1（750 ± 73至572 ± 39）、ICAM（405 ± 26至196 ± 10）和单核细胞趋化因子1蛋白（560 ± 56至423 ± 35）的循环浓度（方差分析均为p <0.01），但不降低E-选择素。在单变量分析中，低密度脂蛋白是氯沙坦治疗后内皮功能和FMD变化的最强预测因子。基线内皮功能与氯沙坦治疗后FMD的变化呈负相关（r2=-0.75，p = 0.0003）。基线ICAM水平单独与低密度脂蛋白胆固醇显著相关（r2= 0.54，p = 0.02），与总胆固醇弱相关（r2= 0.47，p = 0.05）。因此，持续6周的氯沙坦给药对健康老年受试者的炎症标志物具有有利的作用，但不改变外周管道内皮功能。
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.
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DOI：
10.1016/s0735-1097(99)00537-9
发表时间：
2000-01-01
影响因子：
24
作者：
Anderson, TJ;Elstein, E;Charbonneau, F
通讯作者：
Charbonneau, F
影响因子：
15.9
作者：
VAUGHAN, DE;LAZOS, SA;TONG, K
通讯作者：
TONG, K
影响因子：
37.8
作者：
Shih-Jen Hwang;C. Ballantyne;A. Sharrett;L. Smith;C. Davis;A. Gotto;E. Boerwinkle
通讯作者：
Shih-Jen Hwang;C. Ballantyne;A. Sharrett;L. Smith;C. Davis;A. Gotto;E. Boerwinkle
细胞间粘附分子 (ICAM-1) 和发生动脉粥样硬化疾病的风险。
影响因子：
39.3
作者：
Ridker Pm
通讯作者：
Ridker Pm
影响因子：
168.9
作者：
Pitt, B;Poole-Wilson, PA;Thiyagarajan, B
通讯作者：
Thiyagarajan, B