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The steroid aldosterone plays a major role in the maintenance of total body sodium homeostasis and also contributes to cardiovascular pathophysiology by mediating cardiac hypertrophy and fibrosis. In addition to classical adrenal production of aldosterone, endogenous tissue production of aldosterone has been observed in various organs; aldosterone biosynthesis in cardiac tissues, however, remains highly controversial. The current study provides a comprehensive evaluation of steroid hormone biosynthethic capabilities in multiple tissues from two distinct rat strains under unstimulated and stimulated conditions. Panels of tissues from Wistar and Sprague-Dawley rats were probed for 11 beta-hydroxylase (P45011beta) and aldosterone synthase (P450aldo) by reverse transcriptase-polymerase chain reaction (RT-PCR). Under unstimulated conditions, cardiac P45011beta and P450aldo were detected only in Wistar rats. Angiotensin II (100 microg/day) stimulated myocardial expression of both enzymes in both strains. Cerebral cortex and mesenteric artery message levels in both strains was reduced by angiotensin II. These data demonstrate the potential for local steroid synthesis in vascular, cardiac, renal, and neuronal tissues, and that biosynthesis of non-adrenal aldosterone may be differentially regulated between strains. This variability may thus resolve in part or whole the current controversy over the existence of non-adrenal steroidogenic systems.

The classical mineralocorticoid effect of aldosterone on unidirectional transepithelial sodium transport in the kidney was long thought to be the predominant effect of this hormone. However, there is convincing evidence for additional extrarenal actions of aldosterone that are mediated via activation of mineralocorticoid receptors (MRs) in the heart, vasculature and brain. It is now postulated that many of the detrimental effects of aldosterone are mediated through MR activation in these nonclassical target organs. The selective aldosterone blocker, eplerenone (Inspra), is under development for human therapeutic use for treatment of hypertension and heart failure post-myocardial infarction (MI). Clinical and preclinical studies have linked elevated aldosterone to hypertension, left ventricular and vascular remodeling, cardiac, renal, and cerebral vascular inflammation and injury, and increased risk of mortality in heart failure patients. Multiple studies in experimental models of hypertension and heart failure demonstrate that selective blockade of aldosterone by eplerenone effectively preserves cardiac function, attenuates maladaptive left ventricular remodeling and tissue and vascular injury in part by reducing vascular inflammation in aldosterone target organs.