HYPERTENSION CENTER--SCOR

这项多学科的SCOR研究人类的病因、机制和治疗。 高血压。SCOR之前的两次拨款定义了 肾素-血管紧张素-醛固酮轴作为血压和 电解质平衡，并揭示了高血压的异质性。 我们第一次演示了肾素系统的积极参与 在很大一部分高血压患者中，并显示出特异性 抗肾素系统治疗是一种重要的抗高血压新策略。 这一新的SCOR将建立在这一知识的基础上。基础生物化学研究将 研究前肾素和血管紧张素受体，它们是人们最不了解的成分 在分子水平上。特定的抗体将为 对这些分子进行鉴定和量化。他们对世界经济的贡献 高血压的发病机制将在动物模型中进行研究。可能的 激肽释放酶与肾素-血管紧张素系统的联系 将检测来自原肾素的肾素。 使用肾素图谱和我们的血管收缩容量假说，我们将定义 妊娠中毒和胶原血管疾病的升压机制。 在原发性高血压的肾素亚组中，我们将评估其病因 血液粘度、儿茶酚胺的变化与心脏功能的关系 对运动和连续24小时血压波动的影响 监控。心脏病理生理学将使用超声心动图和 核素血管造影术。肾素和醛固酮的分泌机制和 他们与ACTH-皮质醇的相互作用将在肾素亚群中进行研究。 我们对关键规范数据的获取也将使我们能够应用肾素 在定义的一般人群中进行概况分析，以解决以下重要问题 压力以外的因素是否是风险的决定因素，是否与 设计更合理的疗法。 因此，在SCOR上将(1)扩展关于生物化学和生理学的知识 肾素-血管紧张素-醛固酮系统，以及(2)利用 肾素轴的参与，以评估其他变量在 高血压的异质性谱。

This multidisiplinary SCOR studies causes, mechanisms, and treatments of human hypertension. The two previous SCOR grants defined the renin-angiotensin-aldosterone axis as a control system for blood pressure and electrolyte homeostasis and revealed a heterogeneity of essential hypertension. We demonstrated for the first time the active participation of the renin system in substantial fractions of essential hypertension, and showed that specific anti-renin system therapy is an important new antihypertensive strategy. This new SCOR will build on this knowledge. Basic biochemical studies will investigate prorenin and the angiotensin receptor, components least understood at the molecular level. Specific antibodies will provide probes for identification and quantification of these molecules. Their contribution to the pathogenesis of hypertension will be studied in animal models. The possible link of kallikrein to the renin-angiotensin system by regulating biosynthesis of renin from prorenin will be examined. Using renin profiling with our vasoconstriction-volume hypothesis we will define pressor mechanisms of toxemias of pregnancy and of collagen vascular diseases. Within renin subgroups of essential hypertension we will evaluate the pathogenic relation of changes in blood viscosity, catecholamines, and cardiac performance to blood pressure fluctuations of exercise and during continuous 24 hour monitoring. Cardiac pathophysiology will be defined using echocardiograpy and radionuclide angiography. Mechanisms for renin and aldosterone secretion and their interactions with ACTH-cortisol will be studied within renin subgroups. Our acquisition of key normative data also will allow us to apply renin profiling in a defined general population to approach the important questions of whether factors besides pressure are determinants of risk and relevant to designing more rational therapies. Thus, on SCOR will (1) expand knowledge of the biochemistry and physiology of the renin-angiotensin-aldosterone system, and (2) utilize definition of the renin axis' participation to assess the role of other variables in the heterogenous spectrum of hypertension.