This application requests support for an integrated series of studies designed to clarify the mechanisms which relate cell calcium (Ca) to risk of hypertension (Htn) in blacks. Previous research demonstrates a consistent increase in platelet intracellular Ca (Cai) and membrane-bound Ca (Cab) in Htn. Higher intracellular Na (Nai) has been found in blacks than whites, and a stronger association with blood pressure (BP). Nai, Cai, Cab and BP are all inter-correlated in black hypertensives. These findings suggest that cell cations play a causal role in the excess risk of Htn among black patients. Spectrofluorometry and flow-cytometry will be used to extend studies of Cai and Nai. Ca exchange will be measured in platelet membrane vesicles to assess the functional capacity of the Ca-Mg ATPase pump. The Ca pump protein will be purified and characterized in terms of calmodulin affinity, trypsin sensitivity and molecular weight. If alterations in function or structure of this protein are identified, we will determine the frequency of the genes for its isoforms. Participants will be recruited from population-based research, as well as from the clinical setting and whites will be enrolled to permit comparisons. Three generation black families will be recruited for studies of the familial patterns of Htn among blacks. Among individuals at high risk on the basis of abnormalities in Ca metabolism we will further examine: a. The impact of these metabolic traits on Na sensitivity as studied in a randomized trial. b. The potential mediating role of insulin in population surveys. c. The relationships between obesity, insulin and Na sensitivity. d. The potential effect of psychosocial stress. Family pedigrees will be characterized in terms of Htn risk, obesity, insulin resistance, and alterations in Ca metabolism. European admixture will be characterized in the black participants with marker alleles. This research will be linked to on-going studies of blacks in West Africa and the Caribbean. While this research will attempt to address the problem of increased Htn risk among blacks in a comprehensive fashion, the basic goals are focused and complementary. Laboratory research, based firmly on prior experience, will be integrated with population surveys. The mediating effect of the major recognized risk factors will be studied in the context of the biochemical mechanisms. The long-neglected task or studying Htn inheritance in black families will be initiated. If successful, this project should create a level of research sophistication on cation metabolism among blacks equivalent to current efforts in whites, and link US blacks to their populations of origin, as has been accomplished for other US migrant groups.
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