Effect of captopril, MK-421 and MK-422 on fibrinolysis determined by 3 "in vitro" assays.

The effect of captopril, MK-421 and MK-422 on fibrinolysis was investigated in vitro with 3 assay methods. Incorporation of captopril, but not MK-421 and MK-422, into fibrin clots resulted in a reduction of fibrinolysis by purified human plasmin. The concentrations of captopril required to demonstrate this effect far exceeded the therapeutic doses. Pre-mixing plasmin with captopril did not lead to a decreased lysis of fibrin plates. Furthermore, none of these agents affected the lysis of 125I-fibrin plates by a mixture of human serum and streptokinase. Captopril and MK-421, and to a much lesser extent MK-422, inhibited the amidolysis of a fluorogenic synthetic substrate by human plasmin; the inhibition was ameliorated by increasing the substrate concentration. Apparently, the inhibition of fibrinolysis by high doses of captopril, and of amidolysis by captopril and MK-421, appears to lie in their effects on the substrate (fibrin and synthetic substrate) rather than on the enzyme (plasmin).