title: Synergistic antithrombotic effect of a combination of NO donor and plasma kallikrein inhibitor.
abstract: The aim of the present study was to investigate the effect of a NO donor (GSNO) and a plasma kallikrein inhibitor (PKSI-527) alone and in combination on global haemostatic status. A new in vitro test was employed which allows the measurement of both platelet function and spontaneous thrombolysis. Sixteen healthy young and 18 elderly volunteers were enrolled in this study. When GSNO (1 mM) or PKSI-527 (20 microM) was added to native human blood, platelet reactivity was significantly inhibited in both age groups. The combination of GSNO and PKSI-527 had additive inhibitory effect on platelets. Addition of either GSNO or PKSI-527 to blood samples did not significantly affect spontaneous thrombolysis, while added together, spontaneous thrombolysis was significantly enhanced. The thrombolysis enhancing effect was more prominent in elderly subjects. Our present findings suggest that the combination of NO donor and plasma kallikrein inhibitor may have clinical antithrombotic potential.
authors.affiliation: Faculty of Nutrition and High-Technology Research Centre, Kobe Gakuin University, Kobe, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Ikarugi
authors.forename: Ayumi
authors.initials: A
authors.lastname: Inoue
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Yamashita
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tsuda
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Okada
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Ishii
authors.forename: Junichiro
authors.initials: J
authors.lastname: Yamamoto
mesh_terms: D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006801:Humans; D066298:In Vitro Techniques; D007610:Kallikreins / Q000037:antagonists & inhibitors* / Q000097:blood; D008297:Male; D008875:Middle Aged; D020030:Nitric Oxide Donors / Q000008:administration & dosage*; D010649:Phenylalanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D026422:S-Nitrosoglutathione / Q000008:administration & dosage; D013927:Thrombosis / Q000097:blood / Q000517:prevention & control*; D014148:Tranexamic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D005343:Fibrinolytic Agents; D020030:Nitric Oxide Donors; C064866:PKSI 527; D010649:Phenylalanine; D026422:S-Nitrosoglutathione; D014148:Tranexamic Acid; D007610:Kallikreins