M. Wehling et al., NONGENOMIC EFFECTS OF ALDOSTERONE ON INTRACELLULAR CA2-MUSCLE CELLS( IN VASCULAR SMOOTH), Circulation research, 76(6), 1995, pp. 973-979
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.