MECHANISMS AND CONSEQUENCES OF RENAL HYPERTENSION

高血压占终末期肾病的三分之一 黑人(ESRD)和ESRD在黑人中的发病率是黑人的4倍 比白人人口要多。到目前为止，几乎没有证据表明 有效的降压治疗的有效性已经 降低高血压肾硬化症的患病率 ESRD的原因。我们假设原发性高血压是 继发于与以下相关的原发性肾功能障碍 导致肾功能受损的肾功能紊乱 肾功能以适当调节钠的排泄 血压正常。对这一假定的初级知识的理解 肾功能异常是预防高血压肾病的必要手段 疾病。已经建立的肾脏学研究和 这家机构的培训中心寻求成为一名肾脏 中心探索，利用跨学科的基础和临床 调查方法，这一假设的一般和性质 肾脏异常的可能性。激素之间的相互作用 和体液制剂(儿茶酚胺、抗利尿激素、 醛固酮、前列腺素、缓激肽、血管紧张素II等) 可以调节近端小管的钠重吸收， 将检查升肢和皮质集合管。 (项目2、3和8)。肾内肾小球旁结构 将探索控制过滤溶质负荷的机制 利用发育方法和体外分离的 准备工作(项目4)。在必需的动物遗传模型中 高血压和实验性肾性高血压时，肾脏 上皮细胞内氯化钠浓度(电子 微探针)、激素和血管内皮细胞调节 血管反应性、离子转运和体内小管- 在检查肾小球反馈敏感性之前和 在高血压发展之后(项目5、6和7)。在……里面 临床研究，我们将确定高血压是否 作为终末期肾病的原因之一的肾硬化症已经减少了 过去十年；抗高血压药物治疗的前瞻性试验 在经活检证实的肾病患者中将检查 GFR的稳定性(项目1)。最后，我们将调查 环孢素增加肾血管的作用机制 耐药与高血压作为一种药物诱导的原发性高血压模型 人类高血压(项目9)。

Hypertension accounts for one third of end stage renal disease (ESRD) in blacks and ESRD is 4 times more common in the black than in the white population. There is as yet little evidence that the availability of effective antihypertensive therapy has reduced the prevalence of hypertensive nephrosclerosis as a cause of ESRD. We postulate that essential hypertension is secondary to a primary renal disturbance related to derangements in renal function that contributes to an impaired renal capacity to appropriately adjust sodium excretion in a normotensive state. Understanding of this postulated primary renal abnormality is necessary to prevent hypertensive renal disease. The already established Nephrology Research and Training Center at this institution seeks to become a Renal Center to explore, utilizing an interdisciplinary basic and clinical investigative approach, this hypothesis in general and the nature of the renal abnormalities. The interactions among hormones and humoral agents (catecholamines, antidiuretic hormone, aldosterone, prostaglandins, bradykinin, angiotensin II, etc) which may regulate sodium reabsorption in the proximal tubule, ascending limb and cortical collecting tubule will be examined (Project 2, 3, and 8). The intrarenal juxtaglomerular apparatus mechanism to control filtered solute load will be explore utilizing a developmental approach and an isolated in vitro preparation (Project 4). In animal genetic models of essential hypertension and in experimental renal hypertension, renal epithelial intracellular sodium chloride concentrations (electron microprobe), hormonal and endothelial regulation of renal vascular reactivity and ion transport and in vivo tubulo- glomerular feedback sensitivity will be examined before and after the development of hypertension (Projects 5, 6 and 7). In clinical studies, we will determine if hypertensive nephrosclerosis as a cause of ESRD has been reduced over the past decade; a prospective trial of antihypertensive drug therapy in patients with biopsy-proven nephrosclerosis will examine stability of GFR (Project 1). Finally we will investigate the mechanism of cyclosporine-induced increased renal vascular resistance and hypertension as a drug-induced model of essential hypertension in man (Project 9).