V1-VASCULAR VASOPRESSIN RECEPTORS OF MESANGIAL CELL

血管加压素(AVP)不仅是一种有效的抗利尿剂和血管收缩药 激素，但它也刺激血小板聚集，凝血 因子产生、葡萄糖释放和成纤维细胞增殖。全 这些行动可能调解AVP参与发展 动脉高血压和动脉粥样硬化，人类的主要病因 死亡率。 我们致力于AVP研究的长期目标是：1) 血管紧张素转换酶在动脉粥样硬化形成中的作用 高血压素(HTA)与动脉粥样硬化(2)AVP的纯化与克隆 受体，以：a)设计非肽口服活性AVP 用于以AVP诱导的疾病为特征的拮抗剂 血容量、血压和凝血功能的变化，b) 确定抗病的分子缺陷。 肾源性尿崩症中AVP的外周作用。 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 血管紧张素转运蛋白与其特异性膜V1-血管结合后的事件 受体，并隔离任何解释血管增加的变化 遗传高血压大鼠和DOCA-盐性高血压大鼠对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.