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.
Brecher
Arthur S
AS
Department of Chemistry, Bowling Green State University, Bowling Green, Ohio 43403, USA. artbrec@bgnet.bgsu.edu
Murrey
Sarah J
SJ
Gray
Kelly D
KD
Poulimenos
James N
JN
D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology*; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005340:Fibrinogen / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D017706:Lisinopril / Q000494:pharmacology; D010314:Partial Thromboplastin Time; D011107:Polylysine / Q000494:pharmacology; D011517:Prothrombin Time; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000378:metabolism; D013917:Thrombin / Q000187:drug effects / Q000378:metabolism; D013918:Thrombin Time
D000925:Anticoagulants; D000959:Antihypertensive Agents; D004220:Disulfides; D013438:Sulfhydryl Compounds; D011107:Polylysine; D005340:Fibrinogen; D002216:Captopril; D017706:Lisinopril; D013917:Thrombin