Mechanism of plasminogen activator and factor VIII increase after vasoactive drugs

Adrenaline, nicotinic acid (NA), vasopressin (LVP) and other drugs affecting vascular motility are known to increase plasminogen activator (PA) and factor-VIII plasma levels in man. To evaluate the hypothesis that NA, LVP and adrenaline release PA from the endothelial cells of the vessel wall through their common effect on vascular motility, PA has been characterized by means of a histochemical technique on vein biopsies obtained from human volunteers after infusion of the compounds. Furthermore, the effect of single and repeated administration has been compared in order to investigate whether the pattern of PA and factor-VIII variations in plasma is similar with the three drugs. There was no major difference in the PA content of the veins following the marked and sustained increase of the corresponding plasma activities. A simple explanation is that the intensity and duration of the stimulus may not be sufficient to deplete the large stores of the vessel walls. The magnitude, time course and duration of the plasmatic response after single and repeated infusions was on the whole different and peculiar for each drug. A derivative of LVP which is free of vasoactive actions was more effective than LVP in inducing the responses, which could also be elicited in two anephric subjects. These findings suggest that vasoactivity is unlikely to provide the clue to a common pathway for the fibrinolysis and coagulation response after the compounds, and support the existence of different specific receptors.