Physiology
John D Firth, Professor Ian Gilmore in MRCP Part 1 Self-Assessment, 2017
The main stimulus for aldosterone production by the adrenal gland is angiotensin 2, but production is also stimulated by hyperkalaemia. A high level of aldosterone leads to hypokalaemia. The main site of action of aldosterone is the collecting duct, where it binds to a cytoplasmic mineralocorticoid receptor and leads to increased numbers and activity of apical ENaC (sodium) and ROMK (potassium) channels, also of the basolateral Na/K-ATPase. The effect of aldosterone is to simultaneously increase reabsorption of sodium and increase excretion of potassium by the collecting duct. Spironolactone binds to the cytoplasmic mineralocorticoid receptor, preventing the action of aldosterone, and amiloride blocks the ENaC channel. Both therefore reduce the reabsorption of sodium and reduce the excretion of potassium, i.e. they are potassium sparing diuretics.
Endocrine hypertension
Philip E. Harris, Pierre-Marc G. Bouloux in Endocrinology in Clinical Practice, 2014
Although several corticosteroids produced by the adrenal gland have mineralocorticoid function (Figure 21.2), aldosterone is the most potent and predominant human mineralocorticoid. Aldosterone binds to the mineralocorticoid receptor (MR), a nuclear hormone receptor, and causes it to translocate to the nucleus, interact with the respective response elements, and induce a change in transcriptional activity that leads to an increase in activity of the epithelial sodium channel in the distal convoluted tubule (DCT) (Figure 21.3).2 Excess mineralocorticoid results in retention of sodium chloride and water, with obligate loss of potassium and hydrogen ions to maintain electrical neutrality. The resultant clinical picture is of hypertension, metabolic alkalosis, and hypokalemia.
New treatments for hypertension
H. Gavras in The Year in Hypertension 2004, 2004
Drugs that inhibit other peptide systems such as the components of RAAS also represent an important new tool for cardiovascular protection. Angiotensin II stimulates the synthesis of aldosterone, which plays an independent role in cardiovascular damage, inflammation, and fibrosis. Although ACE inhibitors and angiotensin receptor blockers (ARBs or sartans) reduce aldosterone concentrations, aldosterone returns to baseline levels during chronic therapy with ACE inhibitors or ARBs (aldosterone escape). Elevated plasma aldosterone concentrations are associated with endothelial dysfunction, myocardial infarction, left ventricular hypertrophy, and death, and administration of the non-selective mineralocorticoid receptor (MR) antagonist spironolactone enhances the beneficial effect of ACE inhibition, particularly in heart failure. Despite the beneficial effect of spironolactone on mortality in patients with heart failure, the anti-androgenic side effects of spironolactone have limited its usefulness in the treatment of hypertension.
Advances in understanding the role of angiotensin-regulated proteins in kidney diseases
Published in Expert Review of Proteomics, 2019
Ana Belén Sanz, Adrian Mario Ramos, Maria Jose Soler, Maria Dolores Sanchez-Niño, Beatriz Fernandez-Fernandez, Maria Vanessa Perez-Gomez, Marta Ruiz Ortega, Gloria Alvarez-Llamas, Alberto Ortiz
Renin is secreted by kidney juxtaglomerular cells in response to sodium content in the tubular fluid. Renin enzymatic activity processes circulating angiotensinogen to angiotensin I, which in turn is converted to angiotensin II by the angiotensin-converting enzyme (ACE) (Figure 1). The RAS may be activated in the systemic circulation or within tissues. Angiotensin II binds to and activates the angiotensin II type 1 and type 2 receptors (AT1R and AT2R, respectively), among others. Through AT1R activation, angiotensin II promotes vasoconstriction, water intake, sodium retention, and increases oxidative stress, inflammation, fibrosis, and cell growth. This has been termed the classical RAS [6]. A key action is promoting secretion of the mineralocorticoid aldosterone by adrenal glomerulosa cells. Aldosterone activates the mineralocorticoid receptor and promotes sodium reabsorption and potassium secretion in distal tubules, in addition to other actions that promote tissue injury and fibrosis.
Emerging therapeutic strategies for transplantation-induced acute kidney injury: protecting the organelles and the vascular bed
Published in Expert Opinion on Therapeutic Targets, 2019
Nicolas Melis, Raphael Thuillier, Clara Steichen, Sebastien Giraud, Yse Sauvageon, Jacques Kaminski, Thomas Pelé, Lionel Badet, Jean Pierre Richer, Jonatan Barrera-Chimal, Frédéric Jaisser, Michel Tauc, Thierry Hauet
Aldosterone (Aldo) is the main regulator of renal sodium reabsorption, controlling volume and blood pressure levels, through its classical actions on the epitheliums of the distal nephron. Aldo binds to the mineralocorticoid receptor (MR), a transcription factor of the nuclear receptor family present in the kidney and also in non-epithelial cells [88]. Inappropriate mineralocorticoid signaling has been shown to play an important role in the progression of cardiovascular and renal diseases. New extra-renal pathological effects of this hormone have been characterized, extending its deleterious actions to the cardiovascular system [89]. Clinical trials (RALES, EPHESUS, and EMPHASIS-HF) have demonstrated the benefits of administering low doses of MR antagonists to patients with systolic HF with or without myocardial infarction, resulting in improvement of survival rate and morbidity [90,91].
Local ocular renin–angiotensin–aldosterone system: any connection with intraocular pressure? A comprehensive review
Published in Annals of Medicine, 2020
Mervi Holappa, Heikki Vapaatalo, Anu Vaajanen
A mineralocorticoid hormone, aldosterone, is the end product of an RAAS cascade [97]. Ang II as well as Ang III stimulate aldosterone release from adrenal glands which is also the main site of aldosterone synthesis [97,98]. After secretion, aldosterone exerts its effects on sodium and fluid homeostasis via the mineralocorticoid receptor (MR) [21]. However, another endogenous ligand, cortisol, binds to MR with much higher affinity than aldosterone [99]. If the MR is to be activated by its specific ligand aldosterone, then the 11β-hydroxysteroid dehydrogenase type 2 (HSD2) enzyme must be present since it converts cortisol into cortisone, which has much reduced affinity for MR. Together with Ang II, aldosterone stimulates fibrosis, inflammation, cell proliferation, neovascularization and oxidative stress [21,97].
Related Knowledge Centers
- Ligand
- Mineralocorticoid
- Nuclear Receptor
- Signal Transduction
- Heart
- Cell Nucleus
- Large Intestine
- Kidney
- Gene
- Corticosteroid 11-Beta-Dehydrogenase Isozyme 2