SPECIALIZED CENTER OF RESEARCH IN HYPERTENSION

高血压专业研究中心

• 批准号: 3106926
• 负责人: ARAM V CHOBANIAN
• 金额: $ 137.22万
• 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/3106926
• 关键词: cardiovascular disorder prevention; cellular pathology; hypertension; medical complication; 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 提供基础广泛、跨学科的研究方法 发病机制中涉及的细胞和分子机制 高血压的并发症。 该计划的一个主要目标是确定钠的作用， 体液因素及其在病因学中的相互关系 高血压。 这些研究将包括调查： 培养的出租髓质上皮中钠转运的调节 正常血压和高血压的细胞和动脉平滑肌细胞 老鼠； b) 19-去甲脱氧皮质酮对血液升高的影响 人类和实验形式的高血压的压力； c) 的作用 钠泵以及Na、K-亚型的表达和调节 高血压动物模型心脏、动脉和其他组织中的ATP酶； d) 对有明显家族史的高血压患者进行基因研究 确定限制性片段长度是否存在的疾病 最近证明 Na、K-ATP 酶 α-1 亚型的多态性 由我们在达尔盐敏感和自发性高血压中 菌株； e) 血管紧张素II受体的克隆和表征， 它们的组织调节及其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种新的、相对 本实验室制备的缓激肽特异性抑制剂； g) 的 完整动脉和培养血管细胞中的激肽释放酶-激肽系统，以及 该系统组件的表达、它们的调节和响应 高血压； h) V1 和 V2 类加压素的重要性 人类和实验性高血压和心力衰竭的受体 我们已经制备了这些受体的特异性抑制剂 实验室。 研究的另一个重点也是机制 高血压和高胆固醇血症会导致动脉损伤 动脉粥样硬化。 选定的生长因子和的表达 将检查结缔组织成分以确定自分泌 和旁分泌相互作用参与血管疾病的发展。 动脉环功能异常的原因 将评估高血压和高胆固醇血症及其 与 G 蛋白和生长因子变化的关系 决定。 此外，心脏肥大对心脏的影响 结构和功能以及离体心脏的反应 将研究潜在的有害刺激。 高血压 SCOR 应提供有关其病因的重要新知识 和高血压的后果，应该导致针对其的新方法 预防和治疗。