Oxidative stress in aldosteronism

Congestive heart failure (CHF) is more than a failing heart and salt-avid state. Also present is a systemic illness which features oxidative stress in diverse tissues, a proinflammatory phenotype, and a wasting of soft tissue and bone. Reactive oxygen and nitrogen species contribute to this illness and the progressive nature of CHF. Aldosteronism, an integral component of the neurohormonal profile found in CHF, plays a permissive role in leading to an altered redox state. Because of augmented urinary and fecal excretion of Ca²⁺ and Mg²⁺ and consequent decline in plasma-ionized [Ca²⁺]_o and [Mg²⁺]_o that accompanies aldosteronism, parathyroid glands release parathyroid hormone (PTH) in an attempt to restore Ca²⁺ and Mg²⁺ homeostasis; this includes bone resorption. However, PTH-mediated intracellular Ca²⁺ overloading, considered a Ca²⁺ paradox, leads to oxidative stress. This can be prevented by: spironolactone, an aldosterone receptor antagonist that rescues urinary and fecal cation losses; parathyroidectomy; amlodipine, a Ca²⁺ channel blocker; N-acetylcysteine, an antioxidant. In addition to the role played by aldosteronism in the appearance of secondary hyperparathyroidism is the chronic use of a loop diuretic, which further enhances urinary Ca²⁺ and Mg²⁺ excretion, and reduced Ca²⁺ stores associated with hypovitaminosis D. This broader perspective of CHF and the ever increasing clinical relevance of divalent cations and oxidative stress raise the question of their potential management with macro- and micronutrients. An emerging body of evidence suggests the nutritional management of CHF offers an approach that will be complementary to today's pharmaceutical-based strategies.