Thus, in humans with underlying cardiovascular disease or cardiovascular risk factors, vascular MR activation may promote vascular aging and atherosclerosis thereby contributing to the pathophysiology of heart attack, stroke, and possibly even hypertension.
Clinical studies have shown the benefit of MR blockade in patients with left ventricular dysfunction and heart failure after myocardial infarction (MI), hypertension or diabetic nephropathy.
The purpose of this project was to investigate the association of MR gene variants with serum aldosterone and a previously identified hypertension subgroup with higher urinary free cortisol (UFC) levels (high-mode UFC) in a rigorously phenotyped Caucasian hypertensive cohort.
The aim of this study was to evaluate the genotypic distribution of mineralocorticoid receptor and cytochrome P450 11B2 (CYP11B2) T-344C polymorphisms and their relationship with hypertension and cardiac remodeling in a Taiwanese population.
11β-Hydroxysteroid dehydrogenase type 2 (11β-HSD2) catalyzes the inactivation of cortisol (F) to cortisone (E) in aldosterone target tissues, thereby protects mineralocorticoid receptor from F. Failure of 11β-HSD2 function is the basis of apparent mineralocorticoid excess, and its mild disturbances are suggested to lead to hypertension.
Rac inhibition, in addition to mineralocorticoid receptor blockade and salt restriction, would be a new promising strategy for the treatment of salt-sensitive hypertension.
We hypothesized that HDAC inhibition attenuates transcriptional activity of mineralocorticoid receptor (MR) through its acetylation and prevents development of hypertension in deoxycorticosterone acetate-induced hypertensive rats.
Blockers of the renin-angiotensin-aldosterone system (RAAS), that is, renin inhibitors, angiotensin (Ang)-converting enzyme (ACE) inhibitors, Ang II type 1 receptor antagonists, and mineralocorticoid receptor antagonists, are a cornerstone in the treatment of hypertension.
Mineralocorticoid receptor antagonists (MRAs) have effectively been used for the treatment of patients with hypertension who do not have primary aldosteronism (PA).
Inappropriate or over-activation of the mineralocorticoid receptor in ocular cells and other tissues (such as brain, vessels) could link CSCR with the known co-morbidities observed in CSCR patients, including hypertension, coronary disease and psychological stress.
Apparent mineralocorticoid excess (AME) is a rare autosomal recessive disease resulting from mutations within the hydroxysteroid (11β-dehydrogenase2 [HSD11B2]) gene causing a prominent mineralocorticoid receptor activation by cortisol and hypokalemic low renin hypertension as the main clinical feature.
New questions for the next 5 years include a single accepted confirmatory/exclusion test; standardisation of assays and cut-offs; alternatives to universal adrenal venous sampling; reclassification of 'low renin hypertension'; recognition of the extent of 'occult' PA; inclusion of low-dose mineralocorticoid receptor antagonist in first-line therapy for hypertension; and finally, possible resolution of the aldosterone/inappropriate sodium status enigma at the heart of the cardiovascular damage in PA.
CYP3A5 (cytochrome P450, family 3, subfamily A, polypeptide 5) expression stimulates the sodium retentive actions of the mineralocorticoid receptor causative of hypertension, probably by means of its ability to substantially increase the level of 6β-hydroxylase activity.
Steroid hormone aldosterone and its receptor mineralocorticoid receptor (MR) contribute to hypertension by increasing renal salt reabsorption and promote kidney dysfunction through direct effects on renal parenchymal cells.
In this line, the MR antagonists are well-known drugs that display beneficial effects in patients with heart failure and hypertension; it has been proposed that MR antagonists could also play an important role in vascular disease, obesity, obesity-related hypertension, and metabolic syndrome.
In contrast, a MR gain-of-function mutation has been associated with a familial form of inherited mineralocorticoid hypertension exacerbated by pregnancy.
Our data suggest that kidney-specific deficiency of 11β-HSD2 leads to salt-dependent hypertension, which is attributed to mineralocorticoid receptor-epithelial sodium channel-Na<sup>+</sup>-Cl<sup>-</sup> cotransporter activation in the kidney, and provides evidence that renal dysfunction is essential for developing the phenotype of apparent mineralocorticoid excess.
Blockade of MR signaling with MR antagonists (MRAs) has been used clinically to treat kidney and cardiac disease associated with hypertension and other chronic diseases, resulting in suppression of fibrosis in these organs.
The literature is summarized with respect to the role of vascular MR in conditions including: pulmonary hypertension; cerebral vascular remodeling and stroke; vascular inflammation, atherosclerosis and myocardial infarction; acute kidney injury; and vascular pathology in the eye.
Now, 30 years after the cDNA cloning of MR and 60 years of clinical use of steroidal MRAs, novel non-steroidal MRAs such as apararenone, esaxerenone and finerenone are in late-stage clinical trials in patients with heart failure, chronic kidney disease (CKD), hypertension and liver disease.