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Sodium nitroprusside modulates the fibrinolytic system in the rabbit
Author(s) -
Lidbury Paul S.,
Korbut Richard,
Vane John R.
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb14115.x
Subject(s) - sodium nitroprusside , prostacyclin , fibrinolysis , in vivo , ex vivo , plasminogen activator , chemistry , tissue plasminogen activator , platelet , pharmacology , fibrinolytic agent , activator (genetics) , plasminogen activator inhibitor 1 , in vitro , medicine , endocrinology , nitric oxide , biochemistry , biology , microbiology and biotechnology , gene , organic chemistry
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 μg kg −1 ), GTN (30 μg kg −1 ) and prostacyclin (3 μg 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 μg 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 μg 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.