AJP - Heart and Circulatory Physiology, Vol 256, Issue 2 404-H410, Copyright © 1989 by American Physiological Society
Tissue-type plasminogen activator release in response to epinephrine in perfused rat hindlegs
G. J. Zhu, M. Abbadini, M. B. Donati and L. Mussoni
Laboratory for Hemostasis and Thrombosis Research, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
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.
