Aldosterone induces a vascular inflammatory phenotype in the rat heart

Abstract

Vascular inflammation was examined as a potential mechanism of aldosterone-mediated myocardial injury in uninephrectomized rats receiving 1% NaCl-0.3% KCl to drink for 1, 2, or 4 wk and 1) vehicle, 2) aldosterone infusion (0.75 microg/h), or 3) aldosterone infusion (0.75 microg/h) plus the selective aldosterone blocker eplerenone (100 mg. kg(-1). day(-1)). Aldosterone induced severe hypertension at 4 wk [systolic blood pressure (SBP), 210 +/- 3 mmHg vs. vehicle, 131 +/- 2 mmHg, P < 0.001], which was partially attenuated by eplerenone (SBP, 180 +/- 7 mmHg; P < 0.001 vs. aldosterone alone and vehicle). No significant increases in myocardial interstitial collagen fraction or hydroxyproline concentration were detected throughout the study. However, histopathological analysis of the heart revealed severe coronary inflammatory lesions, which were characterized by monocyte/macrophage infiltration and resulted in focal ischemic and necrotic changes. The histological evidence of coronary lesions was preceded by and associated with the elevation of cyclooxygenase-2 (up to approximately 4-fold), macrophage chemoattractant protein-1 (up to approximately 4-fold), and osteopontin (up to approximately 13-fold) mRNA expression. Eplerenone attenuated proinflammatory molecule expression in the rat heart and subsequent vascular and myocardial damage. Thus aldosterone and salt treatment in uninephrectomized rats led to severe hypertension and the development of a vascular inflammatory phenotype in the heart, which may represent one mechanism by which aldosterone contributes to myocardial disease.

Endothelial mineralocorticoid receptor contributes to systolic dysfunction induced by pressure overload without modulating cardiac hypertrophy or inflammation

“…Moreover, aldosterone promotes perivascular inflammation and fibrosis (Rocha et al. 2002). Thus, we next examined whether EC‐MR regulates cardiac fibrosis as a potential mechanism underlying the preservation of systolic function observed in EC‐MR −/− mice in response to TAC.…”

Aldosterone-induced osteopontin gene transcription in vascular smooth muscle cells involves glucocorticoid response element

“…4,5 There is a large body of evidence that Aldo induces inflammatory changes in the vasculature leading to deterioration in vascular function. 6,7 Aldo and sodium load have been reported to cause inflammation and fibrosis in the cardiovascular system. 8,9 However, because the heart and the vasculature do not have enough expression of 11b-hydroxysteroid dehydrogenase type 2, 10 the precise mechanism of how Aldo binds MR and expresses its pro-inflammatory action without glucocorticoid deactivation has not yet been elucidated.…”

Effects of Eplerenone and Salt Intake on Left Ventricular Remodeling after Myocardial Infarction in Rats

“…Aldosterone has been shown to contribute to cardiac fibrosis under salt loading. Regarding the mechanism of this effect, it has been reported that prior to the occurrence of cardiac fibrosis, the infiltration of inflammatory cells such as monocytes and macrophages, and the expression of proinflammatory molecules such as cyclooxygenase-2 (COX-2), monocyte chemoattractant protein-1 (MCP-1), and osteopontin all increased in rats given aldosterone and salt (24). Moreover, eplerenone has been reported to suppress the infiltration of inflammatory cells and the expression of these proinflammatory molecules (6).…”