© 1995 American Heart Association, Inc.
Articles |
Nongenomic Effects of Aldosterone on Intracellular Ca2+ in Vascular Smooth Muscle Cells
From the Baker Medical Research Institute, Victoria, Australia.
Abstract Genomic mechanisms of steroid action have been
increasingly elucidated over the past four decades. In contrast, rapid
steroid actions have been widely recognized only recently, and detailed
analysis of the mechanisms involved are still lacking. The
present article describes rapid effects of mineralocorticoid
hormones on free intracellular calcium in vascular smooth muscle cells
as determined by fura 2 spectrofluorometry in single cultured cells
from rat aorta. These effects are almost immediate and reach a plateau
after only 3 to 5 minutes and are characterized by high specificity for
mineralocorticoids versus glucocorticoids. The potent
mineralocorticoids aldosterone and fludrocortisone are agonists with
estimated apparent EC50 values of 
0.1 to 0.5 nmol/L;
deoxycorticosterone acetate is an agonist with an EC50 of
5 nmol/L; and progesterone, cortisol, corticosterone, and estradiol
have much lower potency (EC50 values of 0.5 to 5
µmol/L). The effect of aldosterone is blocked by neomycin and
short-term treatment with phorbol esters but augmented by
staurosporine, indicating an involvement of phospholipase C and protein
kinase C. The Ca2+ effect appears to involve the
release of intracellular Ca2+, as shown by the
inhibitory effect of thapsigargin; intriguingly, a relatively small
maximum effect (40 nmol/L increase) is consistently seen. This
mechanism operates at physiological subnanomolar aldosterone
concentrations and appears to be a likely candidate for rapid fine
tuning of cardiovascular responsivity. It may also contribute to known
clinical features of mineralocorticoid action that are difficult to
explain by the traditional genomic mechanism alone.
Key Words: free intracellular Ca2+ • aldosterone • nongenomic steroid action • vascular smooth muscle cells
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