Primary autonomic failure is characterized by disabling orthostatic hypotension, but at least half of these patients have paradoxical supine hypertension. Renin-angiotensin mechanisms were not initially thought to contribute to this hypertension because plasma renin activity is often undetectable in autonomic failure. Plasma aldosterone levels are normal, however, and we recently showed that pl...

BACKGROUND It has been suggested that mineralocorticoid receptor antagonists have direct cardioprotective properties, because these drugs reduce mortality in patients with heart failure. In murine models of myocardial infarction, mineralocorticoid receptor antagonists reduce infarct size. Using gene deletion and pharmacological approaches, it has been shown that extracellular formation of the e...

Apparent mineralocorticoid excess (AME) syndrome is a rare autosomal recessive disorder due to the deficiency of 11b hydroxysteroid dehydrogenase type 2 enzyme (11beta-HSD2). Mutations in this gene affect the enzymatic activity resulting to an excess of cortisol, which causes its inappropriate access to mineralocorticoid receptor leading to inherited hypertension.This is a potentially fatal but...

Increased mineralocorticoid levels plus high salt promote vascular inflammation and cardiac tissue remodeling. Mineralocorticoid receptors are expressed in many cell types of the cardiovascular system, including monocytes/macrophages and other inflammatory cell types. Although mineralocorticoid receptors are expressed in monocytes/macrophages, their role in regulating macrophage function to dat...

Rodents exposed to mineralocorticoid excess have considerably decreased taste sensitivity for sodium chloride (NaCl) and show high dietary intake. A similar shift in NaCl perception could be detrimental humans when aldosterone primary aldosteronism (PA) causes hypertension favors consumption. To investigate patients with PA, we studied recognition thresholds as measures of forty PA before after...

BACKGROUND Although aldosterone, acting via mineralocorticoid receptors, causes left ventricular (LV) hypertrophy in experimental models of high-aldosterone hypertension, little is known about the role of aldosterone or mineralocorticoid receptors in mediating adverse remodeling in response to chronic pressure overload. METHODS AND RESULTS We used the mineralocorticoid receptor-selective anta...

The cDNA of the mineralocorticoid receptor (MR) was cloned 30 years ago, in 1987. At that time, spirolactone, the first generation of synthetic steroid-based MR antagonists (MRAs), which was identified in preclinical in vivo models, had already been in clinical use for 30 years. Subsequent decades of research and development by Searle & Co., Ciba-Geigy, Roussel Uclaf and Schering AG toward iden...

C ardiac and renal diseases remain major challenges for healthcare systems in developed countries and commonly coexist, with a disorder in the heart or kidney often leading to secondary dysfunction or injury in the other organ. Indeed, the term cardiorenal syndrome has been introduced to describe the broad spectrum of disease involving both the heart and kidneys. 1 Aldosterone is a steroid horm...

The mineralocorticoid receptor (MR) is descended from a corticoid receptor (CR), which has descendants in lamprey and hagfish, cyclostomes (jawless fish), a taxon that evolved at the base of the vertebrate line. A distinct MR and GR first appear in cartilaginous fishes (Chondrichthyes), such as sharks, skates, rays and chimeras. Skate MR has a strong response to corticosteroids that are mineral...