How does spironolactone work?

Spironolactone was developed to treat edema and hypertension by regulating fluid and electrolyte balance in the kidney.^1,2 Mineralocorticoid receptors in the distal tubule and collecting duct of the kidney bind with aldosterone. Aldosterone increases reabsorption of sodium and excretion of potassium by the kidney, which results in increased salt and water retention, increased blood volume, and increased blood pressure.^3,4 Spironolactone achieves its primary effect by competing with aldosterone for receptor sites in the renal tubules.^1,2 By blocking aldosterone, spironolactone causes fluid and sodium loss and retention of potassium which results in lowered blood pressure.^5–7

Aldosterone has been shown to have far-reaching effects on the cardiovascular, renal, and myocardial tissues that affect cardiac health⁸ and is a factor in the development of resistant hypertension.⁹ It increases vascular tone and promotes collagen synthesis leading to arterial stiffness and increased blood pressure. Studies have found receptors with high affinity for aldosterone in cardiac myocytes and fibroblasts obtained from human hearts.¹⁰ Animal studies suggest that chronic exposure to high aldosterone levels can induce myocardial tissue damage with mechanisms that are independent of blood pressure elevation.^11,12 These studies suggest that the presence of aldosterone over time can induce tissue inflammatory changes¹³ that lead to fibrosis of myocardium¹⁴ that appear to be prevented by administration of aldosterone antagonists.¹⁵

It is probable that spironolactone’s aldosterone-blocking function has a direct beneficial effect on cardiovascular and heart tissue processes.^12,16–18 Although the mechanism of action is not completely understood, as aldosterone receptors have been identified in tissue outside of the renal tubule, including the heart, spironolactone has been used to control other (volume-independent) detrimental cardiac effects of aldosterone, including heart failure and resistant hypertension.^1,9,17

^References

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