Bradykinin receptor antagonism and endothelial tissue plasminogen activator release in humans

Fraser N Witherow, Pamela Dawson, Christopher A Ludlam, David J Webb, Keith A A Fox, David E Newby

Research output: Contribution to journalArticlepeer-review


OBJECTIVE: We sought to assess pharmacodynamic responses to the bradykinin antagonist B9340 and to determine the contribution of the endothelial bradykinin receptor to stimulated tissue plasminogen activator (t-PA) release in humans.

METHODS AND RESULTS: Bilateral forearm blood flow and plasma fibrinolytic variables were measured in 8 volunteers during 100 minutes of intrabrachial infusions of saline placebo, B9340 at 4.5 nmol/min, or B9340 at 13.5 nmol/min. On each occasion, intra-arterial bradykinin (30 to 3000 pmol/min) and substance P (4 to 16 pmol/min) were coinfused for 10 minutes at each dose. To assess the onset and offset of action, 6 additional subjects on 2 occasions received intra-arterial bradykinin (100 pmol/min) for 60 minutes with a coinfusion of either saline placebo or B9340 (13.5 nmol/min) for 12 minutes. During placebo infusion, bradykinin and substance P caused dose-dependent vasodilatation in the infused forearm (P<0.001). B9340 caused a dose-dependent inhibition of bradykinin-induced forearm vasodilatation and t-PA release (P<0.001) without affecting substance P-induced vasodilatation or t-PA release (P=NS). B9340 caused a reversible inhibition of bradykinin-induced vasodilatation (P<0.001) with a rapid onset and offset of action.

CONCLUSIONS: B9340 is a potent, reversible, and selective competitive receptor antagonist of bradykinin-induced vasodilatation and t-PA release in humans.

Original languageEnglish
Pages (from-to)1667-70
Number of pages4
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Issue number9
Publication statusPublished - 17 Jul 2003


  • Adult
  • Bradykinin
  • Bradykinin Receptor Antagonists
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Forearm
  • Humans
  • Infusions, Intravenous
  • Male
  • Regional Blood Flow
  • Research Design
  • Tissue Plasminogen Activator
  • Vasodilation


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