Cellular calcium and sodium regulation, salt-sensitivity and essential hypertension in African Americans

The predisposition of African Americans to the salt sensitive form of essential hypertension may result from increased freely exchangeable Ca in intracellular Ca stores and a higher cellular Ca turnover (i.e., enhanced Ca entry into and accelerated Ca extrusion from the cytosol). These alterations entail higher activities of Ca extrusion transport systems, including the Na+/Ca2+ exchanger (NCE), which extrudes Ca in exchange for external Na+, and plasma membrane Ca-ATPase (PMCA) that extrudes Ca in exchange for external protons. The higher activity of PMCA, coupled with a higher metabolic activity resulting from a rise in freely exchangeable Ca, increase cellular acid load. Adaptive cellular mechanisms must evolve under these conditions, whereby increased activity of the Na/H exchanger (NHE-1) maintains normal cytosolic pH by enhancing the extrusion of cytosolic protons in exchange for extracellular Na. Cells with increased cellular Ca stores and enhanced Ca turnover may be particularly vulnerable to the factors that inhibit the Na-pump. By inhibiting the Na-pump, these factors diminish the transmembrane Na gradient and consequently inhibit the forward mode of the NCE. Since cells from African Americans show increased Ca turnover, they should retain more Ca upon exposure to Na-pump inhibitors; a heightened sensitivity to Na-pump inhibitors could therefore underlie the propensity of African Americans and other individuals with accelerated cellular Ca turnover rate to the salt sensitive form of essential hypertension. Accelerated cellular Ca turnover in African Americans also explains their better response to Ca antagonists compared with other antihypertensive drugs.