Christ M, Douwes K, Eisen C, Bechtner G, Theisen K, Wehling M
Medizinische Klinik, Klinikum Innenstadt, University of Munich, FRG.
Hypertension. 1995 Jan;25(1):117-23. doi: 10.1161/01.hyp.25.1.117.
Increasing evidence has accumulated for rapid nongenomic steroid actions in various cell systems and, more recently, for rapid aldosterone effects on the Na(+)-H+ antiport in human mononuclear leukocytes. The aim of the present study was to demonstrate a rapid, nongenomic aldosterone action in rat vascular smooth muscle cells as a key effector cell in cardiovascular regulation. Basal 22Na+ influx in quiescent vascular smooth muscle cells was 22.1 +/- 1.9 nmol/mg protein per minute (mean +/- SEM, n = 9). Aldosterone (1 nmol/L) stimulated influx to 28.6 +/- 1.5 nmol/mg protein per minute after 4 minutes (n = 9, P < .05), with a half-maximal effect between 0.1 and 0.5 nmol/L; the effects were inhibited by ethylisopropylamiloride, the specific inhibitor of the Na(+)-H+ exchanger, demonstrating the involvement of this transport system in rapid effects of aldosterone. Hydrocortisone (1 mumol/L) was ineffective, and fludrocortisone and deoxycorticosterone increased influx with half-maximal effects at approximately 0.5 nmol/L. Canrenone, a classic antagonist of aldosterone action, did not inhibit stimulation by aldosterone at a 1000-fold excess concentration. Aldosterone significantly stimulated intracellular inositol 1,4,5-trisphosphate levels (P < .05) after 30 seconds; the inhibitors of phospholipase C, neomycin and U-73122, inhibited aldosterone-stimulated Na+ influx and increase of intracellular inositol 1,4,5-trisphosphate. The rapid stimulation of sodium transport in vascular smooth muscle cells and the pharmacological characteristics of this effect are clearly incompatible with the classic, genomic pathway of steroid action and represent further evidence for nongenomic effects of aldosterone.
越来越多的证据表明，在各种细胞系统中存在快速的非基因组类固醇作用，最近还发现醛固酮对人单核白细胞的Na(+)-H+逆向转运体有快速作用。本研究的目的是证明醛固酮在大鼠血管平滑肌细胞中存在快速的非基因组作用，而血管平滑肌细胞是心血管调节中的关键效应细胞。静息血管平滑肌细胞的基础22Na+内流为每分钟22.1±1.9 nmol/mg蛋白（平均值±标准误，n = 9）。4分钟后，醛固酮（1 nmol/L）将内流刺激至每分钟28.6±1.5 nmol/mg蛋白（n = 9，P <.05），半数最大效应浓度在0.1至0.5 nmol/L之间；Na(+)-H+交换体的特异性抑制剂乙基异丙基阿米洛利可抑制该效应，表明该转运系统参与了醛固酮的快速作用。氢化可的松（1 μmol/L）无效，氟氢可的松和脱氧皮质酮可增加内流，半数最大效应浓度约为0.5 nmol/L。醛固酮作用的经典拮抗剂坎利酮在浓度高出1000倍时，并不抑制醛固酮的刺激作用。30秒后，醛固酮显著刺激细胞内肌醇1,4,5-三磷酸水平（P <.05）；磷脂酶C抑制剂新霉素和U-73122可抑制醛固酮刺激的Na+内流以及细胞内肌醇1,4,5-三磷酸的增加。血管平滑肌细胞中钠转运的快速刺激及其药理特性显然与类固醇作用的经典基因组途径不相符，这进一步证明了醛固酮的非基因组作用。
