Sodium nitroprusside modulates the fibrinolytic system in the rabbit.
1. We have investigated the effect of sodium nitroprusside (NP) and glyceryl trinitrate (GTN) on fibrinolysis in anaesthetized rabbits ex vivo and in vitro by measurement of euglobulin clot lysis time (ECLT), plasma levels of tissue plasminogen activator (t-PA) activity, plasma t-PA antigen levels and plasminogen activator inhibitor (PAI-1) activity. 2. In vivo, NP (30 micrograms kg-1), GTN (30 micrograms kg-1) and prostacyclin (3 micrograms kg-1) caused similar transient decreases in left ventricular systolic pressure. However, while prostacyclin induced near-maximal inhibition of ex vivo platelet aggregation, NP or GTN had no effect. 3. Ex vivo, NP caused a significant decrease in ECLT and an increase in plasma t-PA activity. 4. Intravenous co-administration of t-PA (30 micrograms kg-1) with NP caused substantial prolongation of plasma t-PA activity, without affecting t-PA antigen levels. 5. In whole blood in vitro, NP (30 micrograms kg-1) prevented the time-dependent increase in PAI-1 activity and inhibited inactivation of added t-PA (10 ng ml-1). 6. We propose that NP exhibited fibrinolytic activity through increased t-PA activity as a result of inhibition of PAI-1 release from platelets. These results could have important therapeutic consequences when t-PA and nitrate treatments are combined.
Lidbury
P S
PS
William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London.
Korbut
R
R
Vane
J R
JR
D000818:Animals; D011464:Epoprostenol / Q000494:pharmacology; D005342:Fibrinolysis / Q000187:drug effects* / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology*; D015849:Plasminogen Inactivators / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D010959:Tissue Plasminogen Activator / Q000097:blood / Q000494:pharmacology
D015849:Plasminogen Inactivators; D009599:Nitroprusside; D011464:Epoprostenol; D010959:Tissue Plasminogen Activator; D005996:Nitroglycerin