Possible Association of Heart Failure Status With Synthetic Balance Between Aldosterone and Dehydroepiandrosterone in Human Heart

Abstract

Background-Aldosterone is produced not only in the adrenal gland but also in the extra-adrenal tissues, including failing human heart. This study examined the production of dehydroepiandrosterone (DHEA) in human heart and elucidated the possible physiological significance. Method and Results-Using left ventricular tissues obtained at autopsy, reverse transcription-polymerase chain reaction followed by Southern blot analysis revealed the gene expressions of CYP17. By measuring plasma aldosterone and DHEA levels at the coronary sinuses and aortic roots during cardiac catheterization, we found that DHEA but not aldosterone was secreted from control subjects (PϽ0.0001 and Pϭ0.74, respectively), whereas aldosterone but not DHEA was secreted from patients with heart failure (Pϭ0.0017 and Pϭ0.67, respectively). To examine the significance of DHEA, we measured myocyte cell sizes and the gene expression of B-type natriuretic peptide (BNP), using a neonatal rat cardiocyte culture system. We found that DHEA (10 Ϫ8 mol/L) significantly inhibited the increase in myocyte cell sizes and BNP mRNA levels upregulated by endothelin-1 (Pϭ0.031 and PϽ0.0001, respectively). Conclusions-CYP17 gene expression and production of DHEA were demonstrated in human control heart. Also, we found that cardiac production of DHEA was suppressed in failing heart. We postulated that DHEA and/or its metabolites exert a cardioprotective action through antihypertrophic effects.

Cardioprotective Effects of Eplerenone in the Rat Heart

“…9,14,15 Aldosterone perfusion resulted in a rapid rise of the cardiac aldosterone levels, independent of MR. After 30 minutes, the tissue levels (expressed per gram of wet weight) were on average 1.5 times higher than the levels in coronary effluent (expressed per milliliter). Because the extracellular volume in this preparation is Ϸ0.6 mL/g, 23,24 the cardiac aldosterone levels are 2 to 3 times higher than expected if the presence of aldosterone was limited to the extracellular fluid.…”

“…[11][12][13] Across the human coronary vascular bed, both release and uptake of aldosterone have been observed. 14,15 In the present study, using the isolated perfused rat Langendorff heart, we first investigated whether the new and more selective MR antagonist eplerenone exerts the same cardioprotective effects as spironolactone, to additionally unravel whether these effects are MR mediated. Second, we studied the cardiac uptake and washout of circulating aldosterone to determine whether eplerenone, if exerting an MR-dependent effect, interferes with locally synthesized or blood-derived aldosterone.…”

A Review of Age-Related Dehydroepiandrosterone Decline and Its Association with Well-Known Geriatric Syndromes: Is Treatment Beneficial?

“…In fact, the heart produces DHEA in an autocrine way, which decreases as the disease progresses. 102 Low DHEA has been related to a worse prognosis in male patients with chronic heart failure. DHEAS levels were also positively associated with left ventricular ejection fraction, and negatively with amino-terminal pro-brain natriuretic peptide levels.…”

Preconditioning actions of aldosterone through p38 signaling modulation in isolated rat hearts

“…However, the pathophysiological significance of the increase (even by a small amount) in aldosterone levels both in circulation and local tissue, as well as its cascade activation in severe heart diseases (Mizuno et al 2001, Nakamura et al 2004, such as myocardial infarction (Beygui et al 2006), has not yet been fully clarified.…”