Rapid Nongenomic Effects of Aldosterone on Human Forearm Vasculature
Rapid Nongenomic Effects of Aldosterone on Human Forearm Vasculature
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DOI：
10.1161/01.hyp.0000083298.23119.16
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发表时间：
2003-08
期刊：
影响因子：
--
通讯作者：
B. Schmidt;Sebastian Oehmer;C. Delles;R. Bratke;Markus P. Schneider;A. Klingbeil;E. Fleischmann;R. Schmieder
中科院分区：
文献类型：
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作者：
B. Schmidt;Sebastian Oehmer;C. Delles;R. Bratke;Markus P. Schneider;A. Klingbeil;E. Fleischmann;R. Schmieder
摘要--醛固酮在心血管疾病和高血压中的作用最近引起了新的兴趣。醛固酮现在被认为是比以前认为的更常见的高血压原因，并与心肌纤维化有关，与其对高血压的影响无关。最后，除了基因组效应外，快速的非基因组醛固酮效应被认为在高血压中也很重要。48名健康男性志愿者参加了一项随机、安慰剂对照、双盲交叉试验，以阐明醛固酮对人体的快速非基因组血管效应。采用静脉闭塞体积描记法测定前臂血流量。首先，将醛固酮(500 ng/min)和安慰剂注入臂动脉8分钟。然后志愿者接受递增剂量的乙酰胆碱、NG-单甲基-L-精氨酸(L-NMMA)、硝普钠或苯肾上腺素。醛固酮增加前臂血流量(P<；0.001，方差分析)。最大的效果是在8分钟后，醛固酮使前臂血流量增加了7.9±2.6%，而安慰剂组为0.1±1.9%。与安慰剂相比，与安慰剂相比，L-尼莫地平在几分钟内引起更强的血管收缩(P<；0.05，ANOVA)，硝普钠引起的血管收缩减弱(P<；0.01，ANOVA)，苯肾上腺素引起的血管收缩在分钟内加重(P<；0.01，ANOVA)。这些数据表明，醛固酮通过增加血管内皮细胞释放NO和促进血管收缩而在血管平滑肌细胞发挥快速的非基因组作用。这与体外数据显示两种类型的细胞内钙离子增加是一致的。在这两个水平上，这些醛固酮效应的紊乱可能在促进高血压方面起着重要作用。
Abstract—The impact of aldosterone in cardiovascular disease and hypertension has recently gained new interest. Aldosterone is now suggested to be a more common cause of hypertension than previously believed and has been linked to myocardial fibrosis, independent of its hypertensive effects. Finally, rapid nongenomic aldosterone effects have been proposed to be important in hypertension, in addition to its genomic effects. Forty-eight healthy male volunteers were examined in a randomized, placebo-controlled, double-blind crossover trial to elucidate the rapid nongenomic, vascular effects of aldosterone in humans. Forearm blood flow was measured by venous occlusion plethysmography. First, aldosterone (500 ng/min) and placebo were infused into the brachial artery for 8 minutes. The volunteers then received ascending doses of acetylcholine, NG-monomethyl-l-arginine (L-NMMA), sodium nitroprusside, or phenylephrine. Aldosterone increased forearm blood flow (P <0.001, ANOVA). The maximum effect was an increase in forearm blood flow with aldosterone of 7.9±2.6% compared with 0.1±1.9% with placebo treatment after 8 minutes. With aldosterone, L-NMMA induced a greater vasoconstriction (P <0.05, ANOVA), sodium nitroprusside induced an attenuated vasoconstriction (P <0.01, ANOVA), and phenylephrine induced an exaggerated vasoconstriction (P <0.01, ANOVA) within minutes as compared with placebo. These data suggest that aldosterone acts through rapid nongenomic effects at the endothelium by increasing NO release and at the vascular smooth muscle cells by promoting vasoconstriction. This is consistent with in vitro data showing an increase in intracellular calcium in both cell types. Disturbances of these aldosterone effects on both levels might be important in promoting hypertension.