Beta-adrenergic receptor mediated release of tissue plasminogen activator in anaesthetized dogs

Drugs like epinephrine or isoproterenol can enhance fibrinolytic activity of blood. It is still a matter of debate whether this effect can be totally or only partially blocked by beta-receptor blockers. We have developed a dog model for ex vivo measurement of the fibrinolytic activity using a spectrophotometric assay employing human plasminogen, chromogenic plasmin substrate and human fibrinogen-BrCN digests for the stimulation of t-PA. After i.v. administration of isoproterenol the fibrinolytic activity increased, but this could be seen only in the presence of fibrinogen-BrCN digest in the test system. This suggests that isoproterenol caused higher levels of dog t-PA. Pretreatment with the beta-blocker propranolol completely blocked the increase in t-PA.