MECHANISMS OF HYPERTENSION AND RENAL FAILURE IN AFRICAN AMERICANS

患有高血压的非裔美国人(AA)，如果有一名家庭成员患有与高血压相关的终末期肾病(H-ESRD)，也有患肾脏疾病的风险。非洲裔美国人H-ESRD患者的一级亲属是本研究项目的重点。我们将检验以下假设：1)如果肾功能障碍先于高血压，那些肾血流动力学异常的一级亲属比肾血流动力学正常的人更容易患高血压；2)如果高血压先于肾脏疾病，有高血压的一级亲属在观察期内比最初血压正常的人更有可能检测到肾功能下降；3)血压和肾血流动力学变化到盐负荷和耗竭是家族表型，并预测高血压；4)淋巴细胞准确地反映导致容量扩大性高血压的细胞异常；5)糖耐量异常在H-ESRD患者家族中普遍存在；6)长期接触低剂量铅的影响在一些家庭中是相关的，可能会加剧高血压的后果。以下特定目标验证了这些假设：1)评估肾小球滤过率和估计的肾血浆流量；2)评估血压、肾素、醛固酮和淋巴细胞中钠离子流量对盐负荷和盐耗竭的反应；3)葡萄糖和胰岛素对口服葡萄糖负荷的反应；4)评估体内铅的储存；5)储存基因组DNA样本，用于RFLP、微卫星和候选基因座的连锁分析。将有两个对照人群：血压正常的无肾脏疾病高血压家族史的AA和无肾脏疾病家族史的高血压AA。

African Americans (AA) with hypertension who have a family member with endstage 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 abnomality responsible for volume expanded hypertension; 5) Glucose intolerance is prevalent in the families of H-ESRD patients; 6) The influence 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 response 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.