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Nongenomic Effects of Aldosterone on Human Renal Cells

V. Medizinische Universitätsklinik (H.K., B.A.Y., F.J.v.d.W.) and Institute of Clinical Pharmacology (M.C., M.W.), Faculty of Clinical Medicine Mannheim, University of Heidelberg, 68167 Mannheim, Germany; and Department of Internal Medicine IV, J. W. Goethe University (P.C.B.), 60054 Frankfurt am Main, Germany

Address all correspondence and requests for reprints to: Prof. F. J. van der Woude, V. Medical Clinic, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Theodor Kutzer Ufer 1-3, 68167 Mannheim, Germany. E-mail: fokko.van-der-woude{at}med5.ma.uni-heidelberg.de.

The development of chronic renal insufficiency may be partially mediated by the nongenomic action of aldosterone. Here we investigate whether aldosterone could evoke a nongenomic action in primary cultures of human renal cells. Intracellular Ca²⁺ ([Ca²⁺]_i) and cAMP were measured in human mesangial cells (MC), glomerular visceral epithelial cells (GVEC), and proximal and distal tubular epithelial cells (Ptec and Dtec) in the presence of aldosterone (10–100 nmol/liter) by fura-2 fluorescence and RIA, respectively.

In MC, Ptec, and Dtec, aldosterone increased [Ca²⁺]_i within 1 min, whereas in GVEC, only a minor effect was found. Preincubation of cells with spironolactone did not blunt this effect. Hydrocortisone, used at a concentration 100-fold higher than that of aldosterone, did not affect [Ca²⁺]_i. In MC, Ptec, and Dtec, a dose-dependent increase (1.3- to 1.5-fold) in intracellular cAMP levels was found.

These data demonstrate a nongenomic action of aldosterone in human MC, Ptec, and Dtec. As these effects occur at concentrations close to free plasma aldosterone levels in man, they may be of physiological relevance and may contribute to renal injury.

This work was supported by a grant from Deutsche Forschungsgemeinschaft (WO 686/2-1). The results have been presented at the 34th Annual Scientific Meeting of the European Society for Clinical Investigation, Aarhus, Denmark, 2000, as an abstract and at the 32th Meeting of the Deutsche Gesellschaft für Nephrologie, Freiburg, Germany, 1999, as a poster and abstract.

Abbreviations: ACE, Angiotensin-converting enzyme; ATR, angiotensin II receptor; [Ca²⁺]_i, intracellular Ca²⁺; Dtec, distal tubular epithelial cells; FCS, fetal calf serum; fura-2/AM, fura-2/acetoxymethylester; GVEC, glomerular visceral epithelial cells; MC, mesangial cells; PKC, protein kinase C; P/S, penicillin-streptomycin solution; PSS, physiological saline solution; Ptec, proximal tubular epithelial cells; RAAS, renin-angiotensin-aldosterone system.

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