Effect of aspirin on plasminogen activator release in perfused rat hindlegs

The aim of this study was to investigate the effect of aspirin on t-PA release induced by epinephrine in the perfused rat hindlegs model. Epinephrine perfusion (25 μM, 5 min) caused: (a) a rise in perfusion pressure (from 24.9 ± 3.6-182.2 ± 9.5 mmHg; means ± SE); (b) a rise in t-PA activity (from 0.079 ± 0.01-0.180±0.04IU/ ml); (c) an increase in t-PA antigen concentration (from 0.116 ± 0.05-0.248 ± 0.05 ng/ml); and (d) an increase in 6-keto-PGFla level (from 0.160 ± 0.05-0.675 ± 0.05ng/ml). All these effects reached the nadir at the end of perfusion and lasted about 10 min. Aspirin (100mg/kg, iv), administered to rats 60 min previously, while completely inhibiting the release of 6-keto-PGFlα (0.01 ± 0.009ng/ml) did not modify the release of either, t-PA activity (0.180 ± 0.02U/ml) or t-PA antigen levels (0.291 ± 0.05ng/ml) induced by epinephrine administration. The same results were obtained when hindlegs were perfused with aspirin (100 μM) dissolved in Tyrode solution 15 min before epinephrine. The observed lack of effect of aspirin on t-PA release in this study suggests the vascular cyclooxygenase-catalysed pathway of arachidonate metabolism is not involved in t-PA release induced by epinephrine perfusion of rat hindlegs. © 1992.