Central Mineralocorticoid Receptors and Cardiovascular Disease

Abstract

sodium and water by the kidneys [8] became commonly accepted as solely responsible for the hypertension produced by mineralocorticoid + salt excess. Mineralocorticoid Receptors in the Brain Mediate Hemodynamic EffectsThe demonstration of specific binding of aldosterone in select areas of the brain, as well as the heart and vessels [9] , and the finding that the ablation of the anteroventral area of the third ventricle abrogated mineralocorticoid + salt, renovascular and Dahl salt-sensitive (SS) rat hypertension [for a review, see 10 ] kindled interest in the central hemodynamic effects of mineralocorticoids. Selective infusions of mineralocorticoid receptor (MR) agonists and antagonists in various animal models of hypertension confirmed that MR of the circumventricular organs were crucial for the development of several models of hypertension and that activation of MR in the amygdala increased salt appetite [for a review, see 11 ]. Mineralocorticoid Excess Mediates Inflammation and Structural Changes in the Heart, Vessels and KidneysPatients with primary aldosteronism have cardiac hypertrophy compared to patients with essential hypertension who have similar levels of hypertension for the same duration [12,13] . Studies in experimental animals sug- Key WordsMineralocorticoid receptor ؒ Cardiovascular disease ؒ Addison disease, rat model AbstractThe mineralocorticoid receptor (MR) is expressed in many cell types throughout the body, including specific neurons, and mediates diverse functions, many of which are just now being appreciated. MR that pertain to the central modulation of cardiovascular function and health are addressed herein.Copyright © 2009 S. Karger AG, Basel Historical PerspectiveAddison described patients with adrenal cortical destruction as having 'asthenic' hearts over 150 years ago. A century later deoxycorticosterone became the first effective treatment of Addison disease [1] ; however, it was soon recognized that overzealous replacement led to hypertension and renal damage [2] and that it increased vascular responses to epinephrine and norepinephrine in healthy people [3] . Within a few years aldosterone, the primary mineralocorticoid, was isolated [4] , and primary aldosteronism (Conn's syndrome) was described as associated with refractory hypertension and hypokalemia leading to heart and kidney failure [5] . Notwithstanding early evidence of cardiovascular effects [3,6,7] occurring before the appearance of hypertension, the retention of gested that the inflammation leading to fibrosis and hypertrophy of the heart, vessels and kidneys associated with systemic mineralocorticoid + salt excess were mediated by MR in these tissues independently of significant increases in blood pressure [14][15][16][17] . The assumption that 'end organ' pathology is totally independent of hypertension has been contested [18] . MR are prominently expressed in the macrophages, important components of the inflammatory response that migrate into tissue and produce inflammatory cytokines soon after injury, as well as be...

Assessment of Mean Platelet Volume in Patients with Resistant Hypertension, Controlled Hypertension and Normotensives

“…Furthermore it was demonstrated that individuals with RHT without primary hyperaldosteronism have higher aldosterone levels than normal population [22]. The adverse effect of aldosterone excess causes sympathetic activation by stimulation of mineralocorticoid receptors in the paraventricular nuclei [23]. The effects of an over-activated sympathetic nervous system on the haemostatic system occur in two ways.…”

Role of mineralocorticoid action in the brain in salt‐sensitive hypertension

“…Autoradiographic studies have demonstrated a distinctive pattern of binding of aldosterone in the brain, including in those areas identified by ablation studies to be crucial for the development of mineraolcorticoid excess hypertension 9–11 . The chronic administration of aldosterone into the lateral ventricle (i.c.v.)…”

Forebrain corticosteroid receptors promote post-myocardial infarction depression and mortality

“…Ablation (KO) of limbic (forebrain) mineralo-and glucocorticoid receptors (MR/GR)-which have been associated with depressive states clinically-increase the experimental vulnerability toward stress-induced depression with subsequent sympathetic inhibition and increased parasympathetic (X) tone with systemic and cardiac catecholamine (nor-/epinephrine) depletion and elevated ventricular tachycardias (VTs). This finding may explain increased mortality of heart failure patients suffering from depression and the ineffectiveness of psycho-and pharmacological anti-depressive therapy regarding outcome in the absence of the forebrain MR/GR, a crucial role of the forebrain MR in survival of the acute phase of cardiac ischemia has been observed in rats [18]. Moreover, elevated CS levels are independently associated with mortality in patients suffering from HF [32].…”