HYPERTENSION CENTER SCOR

这一多学科的SCOR研究的原因，机制，和治疗人类 高血压 前两次SCOR赠款定义了 作为血压控制系统的肾素-血管紧张素-醛固酮轴， 电解质稳态，并揭示了原发性高血压的异质性。 我们首次证明了肾素系统的积极参与 在原发性高血压的很大一部分，并显示， 抗肾素系统治疗是一种重要的抗高血压新策略。 新的SCOR将建立在这些知识的基础上。 基础生物化学研究将 研究肾素原和血管紧张素受体，这是人们最不了解的成分 在分子水平上。 特异性抗体将提供探针 鉴定和定量这些分子。 的贡献 将在动物模型中研究高血压的发病机制。 可能的 通过调节血管紧张素的生物合成，将激肽释放酶与肾素-血管紧张素系统联系起来。 将检查来自原肾素的肾素。 使用我们的血管收缩体积假说的肾素谱，我们将定义 妊娠毒血症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，我们将评估其致病性。 血液粘度、儿茶酚胺和心脏功能变化的关系 运动时血压波动和连续24小时血压波动 监测. 将使用超声心动图确定心脏病理生理学， 放射性核素血管造影术 肾素和醛固酮分泌的机制， 它们与促肾上腺皮质激素-皮质醇的相互作用将在血浆蛋白酶亚组内进行研究。 我们获得的关键标准数据也将使我们能够应用肾素 在确定的一般人群中进行特征分析，以探讨以下重要问题： 压力以外的因素是否是风险的决定因素， 设计更合理的治疗方法 因此，在SCOR将（1）扩大生物化学和生理学的知识， 肾素-血管紧张素-醛固酮系统，和（2）利用定义的 肾素轴的参与，以评估其他变量的作用， 异质性高血压谱

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.