Figure 3

Aldosterone/salt treatment (ALDOST) in rats and associated increments in urinary and fecal Ca²⁺ excretion leads to plasma-ionized hypocalcemia with secondary hyperparathyroidism and elevated plasma parathyroid hormone (PTH) levels. In turn, and what is considered a Ca²⁺ paradox, PTH promotes intracellular Ca²⁺ overloading. In the case of cardiomyocytes, this includes increased cytosolic free [Ca²⁺]_i and mitochondrial [Ca²⁺]_m. Ca²⁺-overloaded mitochondria elaborate reactive oxygen species and, together with the ensuing oxidative stress, account for the pathological opening of the mitochondria permeability transition pore (mPTP) and entry of solutes that lead to osmotic swelling and destruction of these organelles. Cardiomyocyte necrosis follows with the escape, or leak, or troponins and a wound-healing response with a replacement fibrosis, or myocardial scarring. Adapted from Whitted AD, et al. Am J Med Sci 2010; 340: 48–53, with permission.