Data from the currently funded proposal (NIH-HL 40006-03) indicate that enhanced vascular reactivity characterizing pregnancy-induced hypertension (PIH) is preceded by insulin resistance and associated abnormalities of platelet intracellular calcium ([Ca2+]i) metabolism early in pregnancy. Blacks have a higher incidence of hypertension, insulin resistance, and cellular cation metabolism abnormalities. Thus, the very high incidence of PIH observed in nulliparous urban black women may be due, in part, to insulin resistance and abnormalities of cell cation metabolism. The studies suggest that insulin attenuates vascular contractile responses to vasoconstrictor agonists, in part, by stimulating cellular Ca2+ extrusion (membrane Ca2+-ATPase). Accordingly, the investigators hypothesize that PIH is characterized by an insulin resistant state early in pregnancy and that this insulin resistance results in decreased ability to regulate cellular Ca2+ transport and a consequent failure of insulin to attenuate vasoactive responses. Thus, the investigators propose to characterize the temporal relationship between insulin resistance and altered cell Ca2+ transport and metabolism in PIH and to determine whether these abnormalities are due to inherited traits manifested as a result of pregnancy or are simply gestationally acquired. Systemic (glucose clamp) and cellular (insulin-receptor function) measures of insulin sensitivity will be followed longitudinally through pregnancy in a population at risk for PIH (young nulliparous urban black women) and related to alterations in platelet and fibroblast [Ca2+]i transport and metabolism and maternal vascular reactivity and smooth muscle [Ca2+]i metabolism at delivery. This will enable the investigators to determine if decreased insulin sensitivity precedes and relates to the development of abnormalities in [Ca2+]i metabolism and enhanced vascular reactivity in PIH. To ascertain if PIH-associated gestational abnormalities of insulin action are intrinsic (genetic) or non-inherited (acquired during pregnancy) the investigators will determine if alterations in cellular insulin sensitivity and [Ca2+]i metabolism in skin fibroblasts of women who develop PIH are lost through serial passage of the cells in culture and whether these alterations persist 6 weeks following delivery. To further delineate any genetic propensity towards developing insulin resistance and altered [Ca2+]i metabolism in PIH, the investigators will study the concordance of these abnormalities between PIH patients and their first and second degree maternal relatives.
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