ENHANCED VASCULAR PLASMINOGEN-ACTIVATOR (T-PA) RELEASE BY EPINEPHRINEIN AGED RATS

Adrenergic stimulation induces an acute fibrinolytic response in the v ascular wall and can play an important role in limiting thrombus growt h. The incidence of thrombotic disease increases with age. As many adr energic functions are affected by aging, the vascular response to adre nergic stimulation was studied in young (3 +/- 1 months) and aged (18 +/- 3 months) rats, using an experimental model of vascular perfusion. Hive min epinephrine (EPI) infusion (0.15-25 mu M) induced a dose-dep endent increase in tissue-type plasminogen activator (t-PA) release an d in perfusion pressure, in both young and aged rats. In the latter, h owever, the basal activity of t-PA was significantly higher than in yo ung 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 i n t-PA activity (0.78 +/- 0.06 vs 0.47 +/- 0.08 U/ml, p < 0.01, for 6. 25 mu M EPI), The response was characterized by a delayed onset. In co ntrast, the increase in the perfusion pressure by EPI was significantl y 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, dur ing 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 age d 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 stimulatio n was greater in aging. This response was specific for adrenoceptor st imulation and could represent an adaptative mechanism of adrenergic re ceptors, counteracting an increased thrombotic tendency.