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The epithelial sodium channel (ENaC), (also known as amiloride-sensitive sodium channel) is a membrane-bound ion channel that is selectively permeable to sodium ions (Na +).It is assembled as a heterotrimer composed of three homologous subunits α or δ, β, and γ, [2] These subunits are encoded by four genes: SCNN1A, SCNN1B, SCNN1G, and SCNN1D.
Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. [4] [5] It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. [6]
Potassium-sparing diuretics act to prevent sodium reabsorption in the collecting tubule by either binding ENaCs (amiloride, triamterene) or by inhibiting aldosterone receptors (spironolactone, eplerenone). This prevents excessive excretion of K + in urine and decreased retention of water, preventing hypokalemia. [10]
Although only a fragment of total reabsorption happens here, it is the main part of intervention. This is e.g. done by endogenous production of aldosterone, increasing reabsorption. Since the normal excretion rate of sodium is ~100mmoles/day, then a regulation of the absorption of still more than 1000 mmoles/day entering the collecting duct ...
In physiology, aldosterone escape is a term that has been used to refer to two distinct phenomena involving aldosterone that are exactly opposite each other: Escape from the sodium -retaining effects of excess aldosterone (or other mineralocorticoids ) in primary hyperaldosteronism , manifested by volume and/or pressure natriuresis .
A mineralocorticoid receptor antagonist (MRA or MCRA) [1] or aldosterone antagonist, is a diuretic drug which antagonizes the action of aldosterone at mineralocorticoid receptors. This group of drugs is often used as adjunctive therapy, in combination with other drugs, for the management of chronic heart failure .
On one hand, mutations on the gene NR3C2 (coding the mineralocorticoid receptor) cause the synthesis of a non-functional receptor which is unable to bind aldosterone or function correctly. In the kidney, aldosterone plays an important role of regulating sodium and potassium homeostasis by its actions on distal nephron cells. [3]
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