title: Anticoagulant activity of captopril.
abstract: 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.
authors.affiliation: Department of Chemistry, Bowling Green State University, Bowling Green, Ohio 43403, USA. artbrec@bgnet.bgsu.edu
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Brecher
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Murrey
authors.forename: Kelly D
authors.initials: KD
authors.lastname: Gray
authors.forename: James N
authors.initials: JN
authors.lastname: Poulimenos
mesh_terms: 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
chemical_list: D000925:Anticoagulants; D000959:Antihypertensive Agents; D004220:Disulfides; D013438:Sulfhydryl Compounds; D011107:Polylysine; D005340:Fibrinogen; D002216:Captopril; D017706:Lisinopril; D013917:Thrombin