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剂

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.