THE EFFECTS OF PHYSIOLOGICAL CONCENTRATIONS OF VASOPRESSIN ON COMPONENTS OF THE FIBRINOLYTIC PATHWAY

Abstract

Evidence from studies in man suggests that vasopressin (aVP) at physiological concentrations activates the coagulation pathway, increases plasminogen activator activity and may have a role in the regulation of haemostasis under conditions of physical stress. Infusion of aVP in normal subjects increases plasma factor VIII concentrations and shortens the euglobulin clot lysis time (ECLT), but the mechanisms involved in these changes and their haemostatic significance are unclear. The aims of this study were to investigate the effects of aVP on the fibrinolytic pathway and to evaluate whether thrombin or plasmin are generated in vivo by aVP. After 30 min 0.9% saline infusion, vasopressin (20iu in 250ml 0.9% saline) was infused at 2.0 u/h for 1h in 9 normal subjects to achieve plasma aVP concentrations comparable to those attained during stress. Venous blood samples were taken before saline infusion (time 0) and every 30 min for 2h for assay of aVP, activated partial thromboplastin time (APTT), fibrinopeptide A (FPA), FPA generation time, FPBB15-42 ECLT, tissue-type plasminogen activator (t-PA) and t-PA inhibition. Plasma aVP rose frcm 0.5 pg/ml at time 0 to (median) 70.7 pg/ml at 90 min. The APTT shortened from 43.8 ± 1.9 to 34.4 ± 1.6 (SEM) seconds (p < 0.001) at 90 min. Plasma FPA and the FPA generation time remained unchanged (p > 0.05). Plasminogen activator activity rose from 36.4 ± 15.2 to 587.5 ± 206.6 units (p < 0.005), t-PA increased frcm 229.8 ± 20.4 to 1107.4 ± 224.1 ml.U/ml (p < 0.005) and t-PA inhibition fell frcm 7.9 ± 1.1 to 3.9 ± 0.9 I.U/ml (p < 0.05) in response to the aVP infusion. FPB815-42 increased frcm a baseline value of 1.7 ± 0.4 to 2.2 ± 0.7 pmol/ml after 90 min (p < 0.05). The results suggest the effects of aVP on fibrinolysis are due to an increase in t-PA and decrease in t-PA inhibition. The increase in FPBB 15-42 with no change in FPA supports the hypothesis that plasmin was generated by non-fibrin dependent pathways.