Non-Genomic Effects of Aldosterone on Intracellular Ion Regulation and Cell Function in the Heart

ABSTRACT

Serum aldosterone levels are often elevated in patients with heart failure and are associated with poor clinical outcomes. Aldosterone can be produced in extra-adrenal tissues including the heart, and the local increase in aldosterone exerts deleterious effects on heart structure and function. Aldosterone has 2 types of effects on intracellular ion milieu and cellular function. One is the classical genomic effect in which aldosterone combines with the intracellular mineralocorticoid receptor, transfers to the nucleus, and stimulates synthesis of various proteins. Another is the non-genomic effect that expresses within minutes without synthesizing proteins. The non-genomic effects of aldosterone are less proved in the heart, but it has been shown that aldosterone rapidly activates Na⁺ influxes via Na⁺-K⁺-2Cl^- co-transport and Na⁺/H⁺ exchange, resulting in an increase in intracellular Na⁺ concentration and intracellular alkalinization. These changes in intracellular ion milieu cause positive inotropy, cell swelling, and generation of reactive oxygen species. Thus, the nongenomic effects of aldosterone may contribute, in concert with the genomic effects, to cardiac hypertrophy, fibrosis, and remodeling. This review will discuss the experimental studies examining the mechanisms and physiological/pathophysiological relevance regarding the non-genomic effects of aldosterone in the heart.

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