Schmidt Bernhard M W, Sammer Ulla, Fleischmann Ingrid, Schlaich Markus, Delles Christian, Schmieder Roland E
Department of Nephrology and Hypertension, University of Erlangen-Nuremberg, Erlangen, Germany.
Hypertension. 2006 Apr;47(4):650-5. doi: 10.1161/01.HYP.0000205224.58715.cc. Epub 2006 Mar 6.
There is increasing evidence for the importance of rapid nongenomic effects of aldosterone on the human vasculature. In vitro animal experiments in renal arterioles also suggest the presence of such effects on the renal vasculature. We conducted a clinical study to explore these effects in vivo in humans. Thirteen healthy male volunteers were examined. Aldosterone (500 microg) or placebo was injected intravenously with or without coinfusion of N(G) monomethyl-L-arginine (L-NMMA) in a randomized, double-blinded 4-fold crossover design. Renal plasma flow and glomerular filtration rate were measured by constant infusion clearance technique using inulin and para-aminohippuric acid. Injection of aldosterone without concomitant infusion of L-NMMA changed the renal plasma flow and glomerular filtration rate not statistically significant compared with placebo. Coinfusion of L-NMMA unmasked the effect of aldosterone: aldosterone with L-NMMA decreased the glomerular filtration rate slightly (-1.4+/-6.2 mL/min), whereas infusion of L-NMMA alone increased the glomerular filtration rate (8.3+/-9.8 mL/min; P=0.004). L-NMMA alone decreased renal plasma flow by 58.2+/-97.5 mL/min, and aldosterone with L-NMMA decreased renal plasma flow by 190.0+/-213.7 mL/min (P=0.074). Accordingly, Aldosterone with L-NMMA increased renal vascular resistance much more than L-NMMA alone (1588+/-237 versus 614+/-240 dynxsxcm(-5); P=0.014). These data indicate that aldosterone acts via rapid nongenomic effects in vivo in humans at the renal vasculature. Antagonizing the endothelial NO synthase unmasks these effects. Therefore, rapid nongenomic aldosterone effects increase renal vascular resistance and thereby mediate arterial hypertension if endothelial dysfunction is present.
越来越多的证据表明醛固酮对人体血管的快速非基因组效应具有重要意义。在肾小动脉中进行的体外动物实验也提示存在这种对肾血管的效应。我们开展了一项临床研究以在人体体内探究这些效应。对13名健康男性志愿者进行了检查。采用随机、双盲的4交叉设计，静脉注射醛固酮（500微克）或安慰剂，同时或不同时共输注N(G)单甲基-L-精氨酸（L-NMMA）。使用菊粉和对氨基马尿酸通过持续输注清除技术测量肾血浆流量和肾小球滤过率。与安慰剂相比，单独注射醛固酮且不同时输注L-NMMA时，肾血浆流量和肾小球滤过率的变化无统计学意义。L-NMMA共输注揭示了醛固酮的效应：醛固酮与L-NMMA联合使用时使肾小球滤过率略有降低（-1.4±6.2毫升/分钟），而单独输注L-NMMA则使肾小球滤过率升高（8.3±9.8毫升/分钟；P=0.004）。单独使用L-NMMA使肾血浆流量降低58.2±97.5毫升/分钟，醛固酮与L-NMMA联合使用时使肾血浆流量降低190.0±213.7毫升/分钟（P=0.074）。因此，醛固酮与L-NMMA联合使用时比单独使用L-NMMA更显著地增加肾血管阻力（1588±237对614±240达因·秒/厘米⁻⁵；P=0.014）。这些数据表明醛固酮在人体体内通过对肾血管的快速非基因组效应发挥作用。拮抗内皮型一氧化氮合酶可揭示这些效应。因此，如果存在内皮功能障碍，醛固酮的快速非基因组效应会增加肾血管阻力，从而介导动脉高血压。
