MECHANISMS OF HYPERTENSION AND RENAL FAILURE IN AFRICAN AMERICANS

患有高血压的非裔美国人（AA），并且有家族成员患有糖尿病

African Americans (AA) with hypertension who have a family member with end stage renal disease associated with hypertension alone (H-ESRD) are at risk of also developing renal disease. The first degree relatives of African American H-ESRD patients are the focus of this research project. We will test the following hypotheses: 1) If renal dysfunction precedes hypertension, those first degree relatives who have abnormal renal hemodynamics are more likely to develop hypertension than those with normal renal hemodynamics; 2) If hypertension precedes renal disease, the first degree relatives who have hypertension will be more likely to have detectable declines in renal function over the period of observation than those who were initially normotensive; 3) Changes in blood pressure and renal hemodynamics to salt loading and depletion is a familial phenotype and predicts hypertension; 4) Lymphocytes accurately reflect the cellular abnormality responsible for volume expanded hypertension; 5) Glucose intolerance is prevalent in the families of H-ESRD patients; 6) The influene of chronic exposure to low doses of lead is relevant in some families and may intensify the consequences of hypertension. The following specific aims test these hypotheses: 1) To evaluate glomerular filtration rate and estimated renal plasma flow; 2) To evaluate changes in blood pressure, renin, aldosterone, and sodium fluxes in lymphocytes in reponse to salt loading and depletion; 3) Glucose and insulin response to an oral glucose load; 4) To evaluate body stores of lead; 5) To store genomic DNA samples for RFLP, microsatellite and linkage analysis at candidate gene loci. There will be two control populations: AA who are normotensive without a family history of hypertension of renal disease and AA who are hypertensive without a family history of renal disease.