Tissue-type plasminogen activator release in response to epinephrine in perfused rat hindlegs

We have studied the mechanism of release of plasminogen activator (PA) activity induced by epinephrine in the perfused rat hindleg model. Epinephrine perfusion at the dose of 12.5 microM caused a slighter effect on PA activity but an immediate increase in the perfusion pressure. At 25 microM, epinephrine induced a marked increase in PA activity that reached the maximum level at the end of the drug perfusion. The same response was induced by repeated stimulations with epinephrine (25 microM) only if the second stimulus was given 20-25 min apart from the first one. PA release could be blocked by propranolol (300 microM), a nonspecific beta-blocker, and not by phentolamine, a nonspecific alpha-blocker, unless used at very high concentrations (1,250 microM). Perfusion with dibutyryl adenosine 3',5'-cyclic monophosphate (DbcAMP) alone induces an immediate and transient increase in PA activity, but no potentiation could be demonstrated if theophylline was perfused together with epinephrine. The released PA has been characterized on the basis of molecular weight and immunological criteria as t-PA- and u-PA-like molecules in basal conditions. Epinephrine perfusion induced an increase only in the t-PA-like protein. These data indicate that the release of t-PA-like activity observed after epinephrine perfusion is mainly mediated by beta-receptors and is independent from its vasoactive action.