Anticoagulant Activity of Captopril

The antihypertensive drug, captopril, exerted an anticoagulant effect upon clotting time as followed by prothrombin time (PT) and activated partial thromboplastin time (APTT), with prolongation of clotting observed at 4.25 x 10(-3) M and 4 x 10(-3) M captopril for PT and APTT, respectively, using commercial level I plasma. Utilizing level III plasmas, PT and APTT values were both prolonged by 4.25 x 10(-3) M captopril. Captopril (6 x 10(-3) M) also directly prolonged the clotting of thrombin in a thrombin-factor II-deficient plasma assay, whereas 5 x 10(-3) M captopril inhibited FIIDP in a thrombin-FIIDP assay. In thrombin-fibrinogen assays, pre-incubation of 2.5 x 10(-3) M captopril with fibrinogen also prolonged clotting time, whereas 3 x 10(-3) M captopril prolonged thrombin activity. These data suggest that thiol-disulfide exchange permits reduction of disulfide groups in thrombin and fibrinogen, altering their tertiary structure and physiological function. Lisinopril at a pharmacological 10(-2) M also prolonged APTT, although it lacks a thiol group. Polylysine (1k-4k) affected a prolongation of APTT at 6.7 x 10(-6) M, suggesting inhibition of clotting by a different mechanism.