MECHANISMS OF HYPERTENSION AND RENAL FAILURE IN AFRICAN AMERICANS

患有高血压的非裔美国人（AA），其家庭成员患有终末期高血压 仅与高血压相关分期肾病（H-ESRD） 也有患肾病的风险。 一级亲属 非裔美国人H-ESRD患者是本研究项目的重点。 我们将检验以下假设：1）如果肾功能不全先于 高血压，肾功能异常的一级亲属 血液动力学比那些 肾血流动力学正常; 2）如果高血压先于肾病， 患有高血压的一级亲属更有可能患有高血压， 在观察期间，肾功能的可检测下降， 那些最初血压正常的人; 3）血压的变化， 盐负荷和消耗的肾脏血流动力学是一种家族表型 并预测高血压; 4）淋巴细胞准确地反映了高血压。 导致容积扩张性高血压的细胞异常; 5） 葡萄糖耐受不良在H-ESRD患者的家庭中普遍存在; 6） 长期接触低剂量铅的影响在某些情况下是相关的。 家庭，并可能加剧高血压的后果。 的 以下具体目的验证这些假设：1）评估肾小球 滤过率和估计的肾血浆流量; 2）评价 血压，肾素，醛固酮和淋巴细胞中的钠通量， 对盐负荷和消耗的反应; 3）葡萄糖和胰岛素对 口服葡萄糖负荷; 4）评估铅的体内储存; 5）储存 用于RFLP、微卫星和连锁分析的基因组DNA样本， 候选基因座 将有两个对照人群： 血压正常，无高血压或肾病家族史， 无肾病家族史的高血压AA患者。

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.