Liddle syndrome is a genetically inherited form of hypertension characterized by the overactivity of epithelial sodium channels in the nephron, the functional unit of the kidney. This heightened activity leads to increased sodium reabsorption and excessive excretion of potassium. To counteract this, potassium-sparing diuretics such as amiloride are used. They function by blocking these sodium channels, thereby reducing the influx of sodium into the epithelial cells and minimizing the loss of potassium in the urine. As a result, the sodium concentration in the tubular fluid increases, promoting water excretion and reducing blood volume and pressure. Hypertension can also occur due to overactive kidney β1 receptors or excessive aldosterone production by the adrenal gland. Aldosterone binds to mineralocorticoid receptors (MRs) within the kidney, forming a complex that enters the nucleus and triggers the overexpression of aldosterone-induced proteins like luminal epithelial sodium channels and basolateral sodium-potassium pumps. These proteins are crucial for regulating sodium transport into the bloodstream and potassium out of it, leading to increased blood volume and pressure. Potassium-sparing aldosterone antagonist diuretics bind to these receptors, blocking the complex from entering the nucleus and reducing the expression and activity of the aldosterone-induced proteins. As a result, the blood sodium ion concentration decreases, reducing blood volume without causing potassium loss. However, other diuretic types, like thiazide and loop diuretics, cause hypokalemia or low potassium levels despite being effective hypertension treatments. Thus, potassium-sparing diuretics are often paired with these agents to maintain potassium levels while treating hypertension effectively.
