Enhanced Vascular Plasminogen Activator (t-PA) Release by Epinephrine in Aged Rats

Abstract

SummaryAdrenergic stimulation induces an acute fibrinolytic response in the vascular wall and can play an important role in limiting thrombus growth. The incidence of thrombotic disease increases with age. As many adrenergic functions are affected by aging, the vascular response to adrenergic stimulation was studied in young (3 ± 1 months) and aged (18 ± 3 months) rats, using an experimental model of vascular perfusion. Five min epinephrine (EPI) infusion (0.15-25 μM) induced a dose-dependent increase in tissue-type plasminogen activator (t-PA) release and in perfusion pressure, in both young and aged rats. In the latter, however, the basal activity of t-PA was significantly higher than in young animals (0.22 ± 0.02 vs 0.13 ± 0.01 U/ml; means ± SE; p <0.01, n = 40) and EPI infusion induced a significantly higher increase in t-PA activity (0.78 ± 0.06 vs 0.47 ± 0.08 U/ml, p <0.01, for 6.25 μM EPI). The response was characterized by a delayed onset. In contrast, the increase in the perfusion pressure by EPI was significantly lower in aged that in young rats, its basal levels being normal.To evaluate whether the increased vascular response of t-PA was peculiar for adrenergic stimulation, we infused platelet activating factor (PAF), an inducer of t-PA release, not related to catecholamines. PAF, during five-minute infusion induced a rapid and dose-dependent (100-1250 pM) increase in t-PA release, to the same extent in both young and aged rats.In conclusion, basal t-PA secretion was increased in aged rats probably as a response of vascular endothelium to chronic stimulation. Moreover, the vascular fibrinolytic response to acute EPI stimulation was greater in aging. This response was specific for adrenoceptor stimulation and could represent an adaptative mechanism of adrenergic receptors, counteracting an increased thrombotic tendency.