SPECIALIZED CENTER OF RESEARCH IN HYPERTENSION

高血压专业研究中心

• 批准号: 3106923
• 负责人: ARAM V CHOBANIAN
• 金额: $ 153.38万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-12-15 至 1995-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3106923
• 关键词: disease /disorder model; hypertension; molecular pathology

The Hypertension Specialized Center of Research at Boston University will provide a broad-based and multidisciplinary approach to the study of cellular and molecular mechanisms involved in the pathogenesis and complications of hypertension. A major goal of the program will be to determine the role of sodium, humoral factors, and their interrelationships in the etiology of hypertension. These studies will include investigation of: a) the regulation of sodium transport in cultured rental medullary epithelial cells and arterial smooth muscle cells from normotensive and hypertensive rats; b) the contribution of 19-nor-deoxycorticosterone to elevated blood pressure in human and experimental forms of hypertension; c) the role of the sodium pump and the expression and regulation of the isoforms of Na, K- ATPase in heart, artery, and other tissues of hypertensive animal models; d) genetic studies in hypertensive patients with a strong family history of the disease to determine the presence of a restriction fragment length polymorphism of the alpha-1 isoform of Na, K-ATPase demonstrated recently by us in both the Dahl salt-sensitive and spontaneously hypertensive strains; e) the cloning and characterization of angiotensin II receptors, their tissue regulation, and their potential role in hypertension; f) the role of bradykinin and its interaction with other vaso-active systems in cardiovascular hemodynamics and hypertension utilizing a new, relatively specific inhibitor of bradykinin prepared in our laboratory; g) the kallikrein-kinin system in intact arteries and cultured vascular cells, and the expression of components of this system, their regulation, and response to hypertension; and h) the importance of V1 and V2 classes of vasopressin receptors in human and experimental hypertension and heart failure using specific inhibitors of these receptors which have been prepared in our laboratory. Another major emphasis of the studies also will be on the mechanisms by which hypertension and hypercholesterolemia induce arterial injury and atherosclerosis. The expression of selected growth factors and of connective tissue components will be examined to determine the autocrine and paracrine interactions involved in the development of vascular disease. The cause of functional abnormalities in arterial rings induced by hypertension and hypercholesterolemia will be assessed and their relationship to changes in G-proteins and growth factors will be determined. Furthermore, the effects of cardiac hypertrophy on cardiac structure and function and on the response of isolated hearts to potentially injurious stimuli will be studied. The Hypertension SCOR should provide important new knowledge on the causes and consequences of hypertension and should lead to new approaches on its prevention and treatment.

波士顿大学高血压专业研究中心将 提供一个基础广泛和多学科的方法来研究 参与发病机制的细胞和分子机制， 高血压的并发症。 该计划的一个主要目标是确定钠的作用， 体液因素，以及它们在病因学中的相互关系 高血压 这些研究将包括调查： 培养的肾髓质上皮细胞钠转运的调节 细胞和动脉平滑肌细胞从正常血压和高血压 大鼠; B）19-去甲-脱氧皮质酮对升高的血液 人类和实验性高血压的压力; c） 钠泵与Na，K- 高血压动物模型心脏、动脉等组织ATP酶; d）在具有强烈家族史的高血压患者中进行的遗传研究， 确定是否存在限制性片段长度 Na，K-ATP酶α-1亚型的多态性最近被证实 我们在达尔盐敏感性和自发性高血压 e）血管紧张素II受体的克隆和表征， 它们的组织调节，以及它们在高血压中的潜在作用; f） 缓激肽的作用及其与其他血管活性系统的相互作用 心血管血流动力学和高血压利用一个新的，相对 本实验室制备的缓激肽特异性抑制剂; g） 完整动脉和培养的血管细胞中的激肽释放酶-激肽系统，以及 表达该系统的组成部分，它们的调节和反应 高血压;和h）V1和V2类血管加压素的重要性 受体在人类和实验性高血压和心力衰竭中的应用 我们已经制备了这些受体的特异性抑制剂， 实验室 研究的另一个主要重点也将是机制， 高血压和高胆固醇血症引起动脉损伤， 动脉粥样硬化 选择的生长因子和 将检查结缔组织成分以确定自分泌 以及参与血管疾病发展的旁分泌相互作用。 致动脉环功能异常的原因 将评估高血压和高胆固醇血症， 与G蛋白和生长因子变化的关系将是 测定 此外，心肌肥厚对心脏的影响 结构和功能以及离体心脏对 将研究潜在的有害刺激。 高血压SCOR应提供有关高血压病因的重要新知识 和高血压的后果，并应导致新的方法， 预防和治疗。