(Hypertension. 1995;25:117-123.)
© 1995 American Heart Association, Inc.
Articles |
Rapid Effects of Aldosterone on Sodium Transport in Vascular Smooth Muscle Cells
From the Medizinische Klinik, Klinikum Innenstadt, University of Munich (FRG).
Abstract 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 µmol/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.
Key Words: ion transport • aldosterone • inositol 1,4,5-trisphosphate • carrier proteins • steroids • muscle, smooth, vascular • sodium channels
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