This study will test the hypothesis that, among other factors, the greater predisposition of blacks than whites to essential hypertension relates to innate cellular abnormalities of Na+-K+ transport in the former ethnic group. When present in vascular smooth muscle cells (VSMCs), these genetically determined abnormalities can produce an increase in the peripheral vascular resistance and, consequently, hypertension. To explore this tenet and to exclude the potential effect of extracellular factors, I propose to study in vitro grown, primary and serially passed, skin fibroblasts and VSMCs. The skin fibroblasts will be obtained from both adult and newborn blacks and whites. The VSMCs will be derived from umbilical arteries of the newborn. The following parameters will be studied in these cells: a) the activation of the Na+-K+-APTase (ouabain sensitive ATP hydrolysis) by Na+ and K+, b) the kinetics of 3H-ouabain and K+ binding to the Na+-pump, c) the activity of the Na+-pump (ouabain sensitive 86Rb+ uptake and 22Na+ washout), d) the activity of the Na+, K+-cotransport (bumetanide sensitive 22Na+ and 86Rb+ uptake and washout), e) the activity of the Na+/H+ antiport (amiloride sensitive 22Na+ uptake and washout), f) other non-specific Na+ and K+ transport pathways, and g) the total and exchangeable cellular Na+ and K+ concentrations. These parameters will also be examined with respect to family history of essential hypertension in blacks and whites. By comparing abnormalities identified in cultured VSMCs with those in skin fibroblasts, it will be possible to determine whether they are specific or generalized. Correlations will be made between the various Na+-K+ transport parameters, the cellular Na+ and K+ concentrations and the systemic blood pressure levels. A myriad of factors have direct or indirect influences on cellular Na+ and K+ regulation. As blacks and known to differ from whites in their greater predisposition to essential hypertension and in their handling of Na+ and K+, it is quite possible that they also differ in the manner by which they regulate these ions at the cellular level. This project confronts this possibility in a model of cultured VSMCs and skin fibroblasts. Its finding will be instrumental in elucidating the etiology of essential hypertension in blacks.
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