Schmidt Bernhard M W, Oehmer Sebastian, Delles Christian, Bratke Renate, Schneider Markus P, Klingbeil Arnfried, Fleischmann Erwin H, Schmieder Roland E
Department of Medicine IV/Nephrology, University of Erlangen-Nürnberg, Germany.
Hypertension. 2003 Aug;42(2):156-60. doi: 10.1161/01.HYP.0000083298.23119.16. Epub 2003 Jul 14.
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.
醛固酮在心血管疾病和高血压中的作用最近引起了新的关注。现在认为醛固酮是导致高血压的一个比以前认为的更为常见的原因，并且它与心肌纤维化有关，这与其高血压作用无关。最后，除了其基因组效应外，醛固酮的快速非基因组效应也被认为在高血压中很重要。在一项随机、安慰剂对照、双盲交叉试验中，对48名健康男性志愿者进行了检查，以阐明醛固酮在人体中的快速非基因组血管效应。通过静脉阻塞体积描记法测量前臂血流量。首先，将醛固酮（500 ng/分钟）和安慰剂注入肱动脉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）、硝普钠或去氧肾上腺素。醛固酮增加了前臂血流量（P<0.001，方差分析）。最大效应是醛固酮使前臂血流量增加了7.9±2.6%，而安慰剂治疗8分钟后为0.1±1.9%。与安慰剂相比，使用醛固酮时，L-NMMA在数分钟内引起更大的血管收缩（P<0.05，方差分析），硝普钠引起的血管收缩减弱（P<0.01，方差分析），去氧肾上腺素引起的血管收缩增强（P<0.01，方差分析）。这些数据表明，醛固酮通过在内皮细胞增加一氧化氮释放以及在血管平滑肌细胞促进血管收缩的快速非基因组效应发挥作用。这与体外数据显示两种细胞类型的细胞内钙增加是一致的。醛固酮在这两个水平上的这些效应紊乱可能在促进高血压方面很重要。
