Effect of Aldosterone and Mineralocorticoid Receptor Blockade on Vascular Inflammation

Abstract

Aldosterone, the final product of the renin-angiotensin-aldosterone system, is classically viewed as a regulator of renal sodium and potassium handling, blood volume, and blood pressure. Recent studies suggest that aldosterone can cause microvascular damage, vascular inflammation, oxidative stress and endothelial dysfunction. In animal models, aldosterone-mediated vascular injury in the brain, heart, and kidneys leads to stroke, myocardial injury, and proteinuria. These effects may be modified by dietary salt intake; aldosterone-mediated vascular damage is increased in susceptible animals fed a high-salt diet compared to a low-salt diet despite lower plasma aldosterone levels on the high-salt diet. In humans, there is a growing literature supporting the adverse effects of aldosterone in heart failure, hypertension, left ventricular hypertrophy, and renal disease. Aldosterone receptor antagonists are beneficial even in patients on angiotensin converting enzyme inhibitors and attenuate aldosterone-mediated vascular injury by mechanisms that appear to be independent of changes in systolic blood pressure. This review focuses on the adverse effects of aldosterone on the vascular system and describes our current understanding of the underlying mechanisms for this injury.

Effects of ACE-Inhibitors and Angiotensin Receptor Blockers on Inflammation

“…Similar role is demonstrated for mineralcorticoid receptor (MR) [63]. Specifically, treatment with aldosterone and salt caused extensive inflammatory arterial lesions with perivascular macrophages in the rat heart and increased the expression of ICAM, cyclooxygenase-2, osteopontin, and MCP-1, effects that were decreased by MR blockade [63].…”

“…Several studies have demonstrated that also aldosterone activation induces elevation of oxidative stress and vascular inflammation [63]. Similar role is demonstrated for mineralcorticoid receptor (MR) [63].…”

“…Several animal models have confirmed that aldosterone and other mineralocorticoids can cause injury of the vasculature of the brain, heart and kidneys by inducing ROS formation and endothelial dysfunction [63]. Mineralocorticoid antagonism attenuates this damage by mechanisms that appear to be independent of changes in BP, involving direct pro-inflammatory and pro-fibrotic effects that may involve activation of the ET system [64,65,66,67].…”

Aldosterone activates endothelial exocytosis

“…Hyperaldosteronism is associated with vascular inflammation (1,2,(8)(9)(10)(11)(12)(13)(14). Aldosterone infusion induces leukocyte infiltration into arteries of rats and increases the expression of proinflammatory markers (15,16).…”

Morphological and molecular changes of the myocardium after left ventricular mechanical support

“…An interaction between inflammatory response and activation of neurohormonal systems was suggested [82,83]: animal studies and in vitro experiments have shown that angiotensin II (ATII) activates circulating leucocytes and promotes adhesion to the endothelium, which in response activates adhesion molecules, chemokines and inflammatory cytokines resulting in the production of reactive oxygen species (ROS) and induction of the transcription factor NF-B [84]. Similar observations have been made for aldosterone [85,86]. A series of experimental studies have demonstrated that inflammatory cytokines such as TNF , IL-1 and MCP-1 may directly contribute to the pathogenesis of CHF by inducing contractile dysfunction, ventricular dilation, cardiomyocyte hypertrophy, apoptosis and fibrosis [87][88][89].…”