SCOR IN HYPERTENSION

这个多学科的SCOR检查原因，后果和治疗 人类高血压。 在4个先前的SCOR中，我们表征了肾素- 血管紧张素-醛固酮轴作为调节血液的控制系统 压力，钠容量和钾稳态，并定义其 涉及恶性和肾血管性高血压和双侧 肾上腺皮质增生 使用肾素-钠分析，生化 描述了原发性高血压的异质性， 血浆肾素水平与中、高肾素表型高血压的关系 证明和它的反馈抑制显示在低肾素，钠， 体积表型 这些数据使我们产生了抗肾素系统的概念 药物作为诊断和治疗策略。 本SCOR建立在这些知识和专业知识的基础上。 一个中心主题是 人类高血压的肾脏基础 我们将研究我们的概念， 肾单位异质性，即，低滤过高肾素 和自适应超滤低肾素肾单位，作为异常的基础， 肾素/钠（血管收缩-容积）关系， 高血压 在人类和动物的系统、器官和细胞水平上， 将研究肾单位功能的异质性，血管紧张素II受体， 肾组织的肾素抑制性和肾储备功能。 前肾素作为血管紧张素Ⅱ受体的作用 将检查旁分泌肾内肾素系统的介质。 的 将表征肾素基因表达和生物合成的调节。 该方案的一个重点是发展综合 动态地将前肾素、肾素、血管紧张素II和 醛固酮ANF，钙激素和其他肾上腺类固醇， 饮食中钠和钾的摄入量发生了变化。 这些数据将使 我们研究的意义之间的关系，肾素，心钠素和 其他激素在高血压和妊娠毒血症。 我们将 研究白色被毛高血压的机制，并将其作为一种 心脏损伤的危险因素。 我们将扩大我们的人口研究， 证明血浆肾素是心脏病发作的危险因素， 描述肾素和K+在中风和肾损伤中作用的实验 在动物身上。 心脏功能和LVH作为发病机制的因素， 结果将进一步确定。 总体而言，该计划将定义 高血压的异常机制，并将制定机制标准 来了解靶器官的演变 损害，评估预后和指导治疗。

This multidisciplinary SCOR examines causes, consequences, and treatments of human hypertension. In 4 previous SCOR we characterized the renin- angiotensin-aldosterone axis as a cybernetic system regulating blood pressure, sodium-volume, and potassium homeostasis and defined its involvement in malignant and renovascular hypertensions and in bilateral adrenal cortical hyperplasia. Using renin-sodium profiling, biochemical heterogeneity of essential hypertension was described, the participation of plasma renin in hypertension of medium and high renin phenotypes demonstrated and its feedback suppression shown in the low-renin, sodium- volume phenotype. These data led us to the concept of anti-renin system drugs as a diagnostic and treatment strategy. This SCOR builds on this knowledge and expertise. A central theme is the renal basis for human hypertension. We will investigate our concept of nephron heterogeneity, i.e., discordance between hypofiltering high renin and adaptive hyperfiltering low renin nephrons, as a basis for the abnormal renin/sodium (vasoconstriction-volume) relationships that sustain hypertension. In man and animals at the system, organ and cell levels, we will study heterogeneity of nephron function, of angiotensin II receptors, renal renin supressibility and renal reserve. The role of prorenin as the mediator of a paracrine intrarenal renin system will be examined. The regulation of renin gene expression and biosynthesis will be characterized. A focal point of the program is the development of comprehensive nomographic data dynamically relating prorenin, renin, angiotensin II, and aldosterone to ANF, the calcium hormones and other adrenal steroids as dietary sodium and potassium intakes are changed. These data will enable us to examine the meaning of the relationships between renin, ANF and the other hormones in hypertension and in toxemia of pregnancy. We will examine mechanisms of white coat hypertension and study it further as a risk factor for heart damage. We will extend our population studies that document plasma renin as a risk factor for heart attack, and our experiments describing the role of renin and K+ in stroke and kidney damage in animals. Cardiac performance and LVH as factors in pathogenesis and outcome will be further defined. Overall, this program will define abnormal mechanisms in hypertension and will develop mechanistic criteria other than blood pressure to understand the evolution of target organ damage, assess prognosis and guide treatments.