Cardiac aldosterone production and ventricular remodeling

Abstract

An intracardiac production of aldosterone has been recently reported in rat. This production is increased both acutely and chronically by angiotensin II, observations suggesting that the heart contains a steroidogenic system that is regulated similarly to the adrenal one. Cardiac production of aldosterone is small compared with that of the adrenal, raising the question of its function in normal conditions. Moreover, the regulation of this synthesis in pathophysiologic states remains unknown. In an analysis of the effects of a one-month myocardial infarction (MI) on the cardiac steroidogenic system, it was observed that aldosterone-synthase mRNA and the aldosterone concentration were increased by 2- and 3.5-fold, respectively, in the noninfarcted part of the rat left ventricle. MI also induced a 1. 9-fold increase in the cardiac angiotensin II level. Losartan prevented these changes, and the MI-induced collagen deposition in noninfarcted area of the left ventricle was reduced by 1.6- and 2. 5-fold by both spironolactone and losartan treatments, respectively. Thus, these observations indicate that MI is associated with tissue-specific activation of myocardial aldosterone synthesis. This activation is mediated by cardiac angiotensin II via the angiotensin II type 1 (AT1) receptor, and the resultant increase of intracardiac aldosterone level may be involved in post-MI ventricular remodeling.

Mineralocorticoid Receptors in Myocardial Infarction

“…Several studies have described the ability of chronic in vivo treatment with spironolactone to diminish myocardial fibrosis in response to MI. 3,4 However, the results of the present study indicate comparatively early ex vivo effects of corticosteroids to enhance tissue injury and apoptosis in response to myocardial ischemia and the ability of spironolactone to oppose these effects and maintain tissue viability.…”

“…In contrast, aldosterone replacement in the face of adrenalectomy typically results in recapitulation of target-organ damage to, or even worse than, the sham-operated control condition. Although previous reports indicate significant myocardial production of aldosterone, 3 more recent studies indicate that the majority of aldosterone found in cardiac tissue is derived from the circulation 10 and is consistent with the ability of adrenalectomy to produce impressive end-organ protective effects. Studies with aldosterone synthase inhibitors further support the importance of aldosterone in target-organ damage.…”

Aldosterone, Through Novel Signaling Proteins, Is a Fundamental Molecular Bridge Between the Genetic Defect and the Cardiac Phenotype of Hypertrophic Cardiomyopathy

“…The observed increased myocardial aldosterone levels in patients with HCM is in accordance with the results of recent studies showing extraadrenal gland synthesis of aldosterone, including studies in cardiac myocytes and fibroblasts and the myocardium of patients with heart failure. 19,27,29,30 In the adrenal glands and cultured cells, expression of CYP11B2 is regulated by a diverse array of factors, including angiotensin II, 31 cAMP, 15 12-lipoxygenase, 32 PKC isoforms, 33,34 and calmodulin-dependent protein kinases. 35 These factors, alone or in combination, are plausible candidates to affect expression of CYP11B2 in HCM hearts.…”

Effects of Aldosterone on the Vasculature

“…Aldosterone may be produced in cardiomyocytes in the heart 27,28 and VSMCs, 4,29 although it is not established whether concentrations achieved are high enough to exert local effects. 30 Indeed, in the rat heart, for example, there is little evidence that aldosterone synthase (CYP11B2) and 11(␤)-hydroxylase (CYP11B1) genes are expressed, because there is either extremely low expression of mRNA or protein for steroidogenic enzymes or they are not found at all.…”