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Aldosterone: a steroid hormone of adrenal cortex, has recently attracted much interest not only due to its great importance in regulation of salt and water balance, but also because of its key role in therapy of cardiovascular and renal pathology. The classical genomic mechanism of molecular action of aldosterone is mediated through interaction with mineral-corticoid receptors. Fast nongenomic pathway of cell signal transduction begins with interaction with hypothetic membrane receptors and includes activation of different kinase cascades. Interference of these two pathways of signal transduction assures abroad spectrum of aldosterone effects depending on the cell type, and also secures multycomponent regulation depending on the need of specific functional and stress situation. This review is dedicated to modern views of mechanisms of aldosterone molecular action, mostly of the level of aldosterone-sensitive segment of kidney nephron.

Developmental changes of mRNA alfa-subunit ENaC abundance in renal cortex of 10-day old and in adult rats and aldosterone (10 nM) influence on it were studied. The mRNA level was lower in young rat renal cortex and there was no aldosterone effect on it within 5 hours and 30 minutes, in contrast to adult rats. Intracellular sodium concentration [Na+ i] measured by fluorescent dye Na+ Green in CCD fragments micro-dissected from the kidneys was lower in fragments from immature kidneys, whereas fast nongenomic of aldosterone (10 nM) was the same at both ages. Aldosterone significantly raised [Na+ i] by 40 and 50% in conditions of low sodium concentration (14 mM) in outer medium in epithelial cells of both type of CCD fragments from 10-day old and adult animals, respectively (p < 0.05). We assume that heterochrony of fast and long time genomic effect takes place in aldosterone molecular mechanism maturation. Fast nongenomic effect on the [Na+ i] appeared earlier compared to delayed genomic effect of aldosterone mediated through the changes of the mRNA alpha-subunit ENaC abundance.

Phosphorylation was shown to lead to a change in the conformational equilibrium toward E1 form associated with a decrease in apparent affinity for the K+ in alpha-1 subunit of the rat kidney Na+, K(+)-ATPase. Rate of transition from E2 to E1 was apparently unaffected by phosphorylation. ATP hydrolysis by the protein kinase C-phosphorylated Na+, K(+)-ATPase shows a decrease in the Vmax and Km for K+.

The effect of aldosterone on the cAMP level, the state of inositol-phosphate pool and the intracellular free Ca2+ activity in the rat kidney, were studied. The cAMP level in the kidney cortex homogenate was not changed after i.p. injection of aldosterone. Reliable changes in the content of inositol-phosphates in the kidney cell suspension was not revealed after aldosterone treatment. A short-term enhancement of the intracellular Ca2+ activity in the isolated distal convoluted and cortical collecting tubules under the influence of aldosterone, was revealed. The participation of the second messenger systems in the realisation of aldosterone effects in kidney and the role of Ca2+ in the mechanism of aldosterone action, are discussed.

Specific binding of aldosterone by crude membrane fraction, the affinity and maximal concentration of cytosolic receptors of aldosterone were studied in the kidney cortex of the Wistar rats as well as the plasma level and adrenal biosynthesis of aldosterone. The specific binding of aldosterone was found to increase in membrane fraction and to decrease in cytosol during kidney maturation. The affinity of the cytosol receptors to aldosterone did not change in the same period. The level of biosynthesis in adrenals and plasma concentration of aldosterone was higher in adult rather than in young rats. The membrane binding of aldosterone seems to take part in the mechanism of cell sensitivity to aldosterone.