Studies of the Blood Plasminogen Activator Induced by 1-Desamino-8-D-arginine Vasopressin with Observations in von Willebrand's Disease 1

Abstract

Abstract

The nature of the blood plasminogen activator released in humans by infusion of the vasopressin analog, 1-desamino-8-D-arginine vasopressin (DDAVP), was studied utilizing an antibody raised against a plasminogen activator purified from the culture medium of a melanoma cell line. The melanoma activator cross-reacted immunologically with tissue plasminogen activator purified from human uterine tissue. The fibrinolytic activity of human blood elicited by DDAVP could be quenched by a melanoma activator antiserum, demonstrating that the vasopressin analog, which lacks vasopressor properties, released a tissue plasminogen activator-related substance to the blood. Urokinase-like material measured by radioimmunoassay, was not released by DDAVP. Nor was the intrinsic fibrinolytic system of plasma affected, since Cl inactivator-sensitive activity was not enhanced. In severe von Willebrand's disease, which is characterized by an endothelial defect of factor VIIIR:Ag synthesis, DDAVP did not release tissue activator into the blood, although the patients had a low resting level of this material. A defective endothelial receptor for DDAVP or some intermediary mediator is suggested in this disease.