Effects of aldosterone and mineralocorticoid receptor blockade on intracellular electrolytes.

Abstract:

:Genomic mechanisms of mineralocorticoid action have been increasingly elucidated over the past four decades. In renal epithelia, the main effect is an increase in sodium transport through activation and de novo synthesis of epithelial sodium channels. This leads to increased concentrations of intracellular sodium activating sodium-potassium-ATPase molecules mainly at the basolateral membrane which extrude sodium back into the blood stream. In contrast, rapid steroid actions have been widely recognized only recently. The present article summarizes both traditional and rapid effects of mineralocorticoid hormones on intracellular electrolytes, e.g. free intracellular calcium in vascular smooth muscle cells as determined by fura 2 spectrofluorometry in single cultured cells from rat aorta. Latter effects are almost immediate, reach a plateau after only 3 to 5 minutes and are characterized by high specificity for mineralocorticoids versus glucocorticoids. 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 Ca(2+) effect appears to involve the release of intracellular Ca(2+), as shown by the inhibitory effect of thapsigargin. This mechanism operates at physiological subnanomolar aldosterone concentrations and appears to result in rapid fine tuning of cardiovascular responsivity. As a landmark feature of these rapid effects, insensitivity to classic antimineralocorticosteroids, e.g. spironolactone or canrenone has been found in the majority of observations. In an integrated view, mineralocorticoids seem to mainly effect intracellular electrolytes genomically to induce transepithelial transport, and induce nongenomically mediated alterations of cell function (e.g. vasoconstriction) by rapid effects on intracellular electrolytes such as free intracellular calcium.

journal_name

Heart Fail Rev

journal_title

Heart failure reviews

authors

Wehling M

doi

10.1007/s10741-005-2347-z

subject

Has Abstract

pub_date

2005-01-01 00:00:00

pages

39-46

issue

1

eissn

1382-4147

issn

1573-7322

journal_volume

10

pub_type

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