V1-VASCULAR VASOPRESSIN RECEPTORS OF MESANGIAL CELL

加压素（AVP）不仅是一种强有力的抗利尿剂和血管收缩剂， 激素，但它也刺激血小板聚集，血液凝固 因子产生、葡萄糖释放和成纤维细胞增殖。 所有 这些作用可能介导AVP参与了 动脉高血压和动脉粥样硬化，人类的主要原因 mortality. 我们致力于AVP研究的长期目标是： 阐明AVP在动脉发育中的作用， 高血压（HTA）与动脉粥样硬化关系; 2）AVP的纯化和克隆 a）设计非肽口服活性AVP 用于特征为AVP诱导的疾病的拮抗剂 血容量、血压和血液凝固的改变，B） 确定耐药性背后的分子缺陷， AVP在肾源性尿崩症中的外周作用 使用人和大鼠肾小球系膜细胞（GMC）培养， 本提案的目标是：1）探索完整的级联 AVP与其特异性膜V1-血管结合后的事件 受体和分离任何改变解释增加的血管 在遗传性和DOCA-盐高血压大鼠中观察到对AVP的反应性。 2)纯化人和大鼠V1血管AVP受体。

Vasopressin (AVP) is not only a potent antidiuretic and vasoconstrictor hormone but it also stimulates platelet aggregation, blood coagulation factors production, glucose release and fibroblast proliferation. All these actions may mediate the involvement of AVP in the development of arterial hypertension and atherosclerosis, the leading causes of human mortality. The long-term objectives of our research dedicated to AVP are: 1) to delineate the role played by AVP in the development of arterial hypertensin (HTA) and atherosclerosis, 2) to purify and clone AVP receptors in order to: a) design non peptide orally active AVP antagonists to be used in diseases characterized by AVP-induced alterations of blood volume, blood pressure, and blood coagulation, b) identify the molecular defect underlying the resistance to the peripheral actions of AVP in the nephrogenic type of diabetes insipidus. Using human and rat glomerular mesangial cells (GMC) in culture, the goals of the present proposal are to: 1) explore the complete cascade of events following binding of AVP to its specific membrane V1-vascular receptors and isolate any alteration explaining the increased vascular reactivity to AVP noted in genetically and DOCA-salt hypertensive rats. 2) purify the human and rat V1-vascular AVP receptors.