NONGENOMIC EFFECTS OF ALDOSTERONE ON INTRACELLULAR CA2-MUSCLE CELLS( IN VASCULAR SMOOTH)

Genomic mechanisms of steroid action have been increasingly elucidated over the past four decades. In contrast, rapid steroid actions have b een widely recognized only recently, and detailed analysis of the mech anisms involved are still lacking. The present article describes rapid effects of mineralocorticoid hormones on free intracellular calcium i n vascular smooth muscle cells as determined by fura 2 spectrofluorome try in single cultured cells from rat aorta. These effects are almost immediate and reach a plateau after only 3 to 5 minutes and are charac terized by high specificity for mineralocorticoids versus glucocortico ids. The potent mineralocorticoids aldosterone and fludrocortisone are agonists with estimated apparent EC(50) values of approximate to 0.1 to 0.5 nmol/L; deoxycorticosterone acetate is an agonist with an EC(50 ) of approximate to 5 nmol/L; and progesterone, cortisol, corticostero ne, and estradiol have much lower potency (EC(50) values of approximat e to 0.5 to 5 mu mol/L). The effect of aldosterone is blocked by neomy cin and short-term treatment with phorbol esters but augmented by stau rosporine, indicating an involvement of phospholipase C and protein ki nase C. The Ca2+ effect appears to involve the release of intracellula r Ca2+, as shown by the inhibitory effect of thapsigargin; intriguingl y, a relatively small maximum effect (approximate to 40 nmol/L increas e) is consistently seen. This mechanism operates at physioiogical subn anomolar aldosterone concentrations and appears to be a likely candida te for rapid fine tuning of cardiovascular responsivity. It may also c ontribute to known clinical features of mineralocorticoid action that are difficult to explain by the traditional genomic mechanism alone.