Effect of Spironolactone on Renal Function in Severe Congestive Heart Failure. Results from the Belgian Rales Substudy

Rousseau, Michel F.; Gurne, Olivier; Ahn, Sylvie A.

doi:10.1016/j.cardfail.2007.06.533

Cited by 1 publication

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“…In both studies, the MR antagonists improved clinical outcomes independently of the effects on blood pressure. The plasma concentration of aldosterone increases up to 0.1 μM in patients with heart failure, and the level of aldosterone in the myocardium is much higher than that in plasma [5,6]. The rapid and direct effects of aldosterone on the heart are, therefore, considered to have significant clinical relevance and to be important as a therapeutic target for heart failure.…”

Section: Introductionmentioning

confidence: 99%

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

Satoh¹,

Matsui²,

Hayashi³

2009

VDP

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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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Section: Introductionmentioning

confidence: 99%