Nongenomic effects of aldosterone on intracellular calcium in porcine endothelial cells.
Rapid in vitro effects of aldosterone on intracellular electrolytes, cell volume, and the sodium-proton antiport have been described in human mononuclear leukocytes and vascular smooth muscle cells. In the present study, we demonstrate rapid aldosterone effects on free intracellular calcium as determined by fura 2 fluorometry in single porcine endothelial cells. After addition of 100 nmol/l aldosterone, cells respond with a sustained rise in free intracellular calcium by approximately 50% of initial levels within 1-5 min. Elevations are predominantly seen in the subplasmalemmal space. Effective half-maximal concentration values for aldosterone are approximately 1 pmol/l and for cortisol approximately 1 nmol/l. These effects are blunted in calcium-free medium and absent after pretreatment by thapsigargine. They remain unchanged by a >1,000-fold excess of spironolactone. These findings indicate the existence of a nongenomic pathway for aldosterone action in porcine endothelial cells and may be related to known rapid cardiovascular effects of aldosterone in vivo mediated through the baroreceptor reflex.
Schneider
M
M
Division of Clinical Pharmacology, Medizinische Klinik, Klinikum Innenstadt, University of Munich, Germany.
Ulsenheimer
A
A
Christ
M
M
Wehling
M
M
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005456:Fluorescent Dyes; D016257:Fura-2; D016678:Genome; D006728:Hormones / Q000494:pharmacology; D006854:Hydrocortisone / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism*; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D013552:Swine; D019284:Thapsigargin / Q000494:pharmacology
D005456:Fluorescent Dyes; D006728:Hormones; D000451:Mineralocorticoid Receptor Antagonists; D000450:Aldosterone; D019284:Thapsigargin; D002118:Calcium; D016257:Fura-2; D006854:Hydrocortisone