MECHANISMS AND CONSEQUENCES OF RENAL HYPERTENSION

肾高血压的机制和后果

• 批准号: 3105869
• 负责人: DAVID Gene WARNOCK
• 金额: $ 73.13万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-01 至 1992-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3105869
• 关键词: hormone regulation /control mechanism; ion transport; renal hypertension; renal tubular transport

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).

高血压占终末期肾病的三分之一 （ESRD）在黑人和ESRD是4倍更常见的黑色 而不是白色人群。 迄今为止，几乎没有证据表明 有效抗高血压治疗的可用性 降低了高血压肾硬化的患病率， ESRD的原因 我们假设原发性高血压是 继发于与以下疾病相关的原发性肾功能紊乱 肾功能紊乱，导致肾功能受损 肾脏适当调节钠排泄的能力 正常血压状态。 对这一假设的理解 肾功能异常是预防肾性高血压的必要条件 疾病 已经成立的肾病研究和 该机构的培训中心旨在成为一个肾 中心探索，利用跨学科的基础和临床 调查方法，这一假设一般和性质 肾功能异常 激素之间的相互作用 和体液剂（儿茶酚胺，抗利尿激素， 醛固酮、肾上腺素、缓激肽、血管紧张素II等）， 可以调节近端小管中的钠重吸收， 将检查升支和皮质集合小管 （项目2、3、8）。 肾内肾小球体 将探索控制过滤溶质负荷机制 利用发育方法和分离的体外 项目（4）。 在动物遗传模型中， 高血压和实验性肾性高血压，肾性 上皮细胞内氯化钠浓度（电子 微探针），激素和内皮调节肾 血管反应性和离子转运以及体内小管- 肾小球反馈敏感性将在术前检查， 在高血压发展后（项目5、6和7）。 在 临床研究，我们将确定是否高血压 肾硬化症作为终末期肾病的原因已经减少， 过去十年;抗高血压药物治疗的前瞻性试验 在活检证实的肾硬化患者中， GFR的稳定性（项目1）。 最后，我们将调查 环孢素增加肾血管生成的机制 阻力和高血压作为一种药物诱导的模型， 人类高血压（项目9）。