Effect of physiological concentrations of vasopressin on components of the fibrinolytic system.
High physiological concentrations of plasma vasopressin (aVP) when achieved by infusion cause an increase in plasma factor VIII coagulant activity and shortening of the euglobulin clot lysis time (ECLT). To investigate the effects of aVP on components of the fibrinolytic pathway and on thrombin generation, 9 healthy volunteers were infused with saline for 30 min followed by aVP for 1 hour and blood samples taken every 30 min for measurement of aVP, ECLT, tissue-type plasminogen activator (t-PA), t-PA inhibition (tPA-I), plasminogen activator inhibitor 1 (PAI-1 Ag), activated partial thromboplastin time (APTT), fibrinopeptide A (FPA), fibrinopeptide B 15-42 (FPB beta 15-42) and cross-linked fibrin breakdown products (XL-FDP). Plasma aVP rose to a median of 75 pg/ml after 90 min and fell to 13.8 pg/ml 30 min later. The APTT fell from 43.5 to 35 sec (p less than 0.01) but there was no change in plasma FPA or in XL-FDP. Plasminogen activator activity (10(6)/ECLT2) increased from 25 to 736 units (p less than 0.01) and t-PA from 200 to 1012 mIU/ml (p less than 0.01). tPA-I fell from 8.0 to 2.7 IU/ml at 90 min (p less than 0.05) but PAI-1 Ag remained unchanged. Plasma FPB beta 15-42 was 2.4 and 1.2 pmol/ml before infusion with aVP and showed a small rise to 3.5 pmol/ml after 60 min (p less than 0.05). The results show the effects of aVP on fibrinolysis are mediated by an increase in t-PA. In the absence of thrombin generation the rise in t-PA was not accompanied by changes in XL-FDP.
Hariman
H
H
University Department of Medicine, General Infirmary, Leeds, UK.
Grant
P J
PJ
Hughes
J R
JR
Booth
N A
NA
Davies
J A
JA
Prentice
C R
CR
D000328:Adult; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005342:Fibrinolysis / Q000187:drug effects*; D005344:Fibrinopeptide A / Q000032:analysis; D005345:Fibrinopeptide B / Q000032:analysis; D006801:Humans; D010314:Partial Thromboplastin Time; D010446:Peptide Fragments / Q000032:analysis; D010940:Plant Proteins; D011480:Protease Inhibitors / Q000032:analysis; D012639:Seeds; D010959:Tissue Plasminogen Activator / Q000032:analysis; D014667:Vasopressins / Q000494:pharmacology*
D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; D010940:Plant Proteins; D011480:Protease Inhibitors; C033786:fibrinogen Bbeta (15-42); C053884:trypsin inhibitor, Erythrina caffra; D014667:Vasopressins; D005344:Fibrinopeptide A; D005345:Fibrinopeptide B; D010959:Tissue Plasminogen Activator