Aldosterone: direct effects on and production by the heart.

Abstract

The main effects of aldosterone, the most physiologically important mineralocorticoid, are on electrolyte transport across epithelia, particularly in the kidney, but also in other tissues, such as salivary glands and colon. Aldosterone acts to increase sodium (and consequently water) resorption and potassium excretion by directly or indirectly increasing the activity of epithelial sodium channels and sodium, potassium-adenosine triphosphatase (1). Aldosterone excess, whether from genetic causes or primary aldosteronism (hyperplasia or aldosterone-secreting adenomas), is well documented to cause hypertension. Hypertension, in turn, has significant adverse effects on the cardiovascular system, including left ventricular hypertrophy and cardiac fibrosis. Clinical evidence has been accumulating at an accelerating rate suggesting that aldosterone has direct adverse effects on the heart that are independent of its effects on blood pressure. Patients with primary aldosteronism are more likely to have left ventricular hypertrophy and stroke than patients with essential hypertension of comparable severity. More importantly, patients with severe heart failure have a 30% reduction in morbidity and mortality when given a mineralocorticoid receptor antagonist, spironolactone, in addition to conventional therapy of an angiotensin-converting enzyme (ACE) inhibitor, digoxin, and furosemide. The dose of spironolactone used in this study (25 mg) had no incremental effect on blood pressure, suggesting a direct cardioprotective effect (2). Remarkably, spironolactone had a significant beneficial effect only in patients with above median baseline levels of a marker of collagen synthesis, procollagen type III amino-terminal peptide. Elevated baseline levels of this peptide were associated with an increased risk of death and hospitalization, and circulating levels were decreased by spironolactone treatment. These results suggest that the limitation of cardiac fibrosis may be one of mechanisms by which spironolactone benefits patients with congestive heart failure (3). The present article reviews recent evidence for direct cardiac effects of aldosterone and synthesis of aldosterone within the heart. Details of the role of aldosterone in congestive heart failure and the use of aldosterone antagonists in treating heart disease can be obtained from other reviews (4).