MineralocorticoidRezeptorAantagonisten

Mineralocorticoids are a class of steroid hormones that regulate electrolyte and fluid balance. In humans, the principal mineralocorticoid is aldosterone, produced by the adrenal cortex’s zona glomerulosa. Other species may rely on corticosterone or deoxycorticosterone to varying degrees for mineralocorticoid activity.

Aldosterone acts primarily on the distal nephron of the kidney, where it binds to the intracellular mineralocorticoid receptor in principal cells. This receptor-ligand complex alters gene transcription, increasing the abundance of apical epithelial sodium channels (ENaC) and basolateral Na+/K+ ATPases. The result is enhanced sodium reabsorption and potassium secretion, with accompanying water retention and changes in acid-base balance. Mineralocorticoid effects also occur in colon and sweat glands, contributing to overall body sodium conservation.

Regulation of mineralocorticoids is tightly linked to the renin-angiotensin-aldosterone system (RAAS). Low blood pressure, low sodium, or high potassium stimulates renin release, increasing angiotensin II production and prompting aldosterone secretion. Adrenocorticotropic hormone has a minor stimulatory role, while cortisol can bind the receptor but is locally inactivated in the kidney to prevent non-specific effects. Aldosterone help maintains extracellular fluid volume and blood pressure.

Clinically, excess mineralocorticoid activity causes primary or secondary hyperaldosteronism, leading to hypertension and hypokalemia. Treatment includes mineralocorticoid receptor antagonists such as spironolactone and eplerenone, used in conditions like resistant hypertension, heart failure, and certain forms of hyperaldosteronism. Deficiency leads to hypoaldosteronism, with hyperkalemia and salt-wasting, seen in adrenal insufficiency. Synthetic and naturally occurring compounds with MR activity contribute to therapeutic and physiological effects.