Physiological Roles of Bradykinin and Involvement of Bradykinin B2 Receptor in Urethral Function in Humans and Animals

Objective We investigated the role of bradykinin in urethral function by examining contractile responses in urethral smooth muscle strips isolated from humans and the intraurethral pressure in rats and dogs. Methods The contractile responses of human urethral tissue for bradykinin (0.01–10 µmol/L) were examined, and changes in intraurethral pressure induced by bradykinin (0.003–10 µg/kg) in anesthetized rats or dogs were measured. In addition, the effects of pretreatment with the bradykinin B2 receptor antagonist FK3657 were also examined. Results In smooth muscle strips obtained from human urethra, bradykinin induced contraction, which was inhibited by FK3657 in a concentration‐dependent manner. In anesthetized rats and dogs, intravenously administered bradykinin dose‐dependently increased intraurethral pressure. FK3657 shifted the intraurethral pressure dose‐response curve for bradykinin to the right in rats. The bradykinin‐induced elevation of intraurethral pressure was also dose‐dependently inhibited by FK3657 in dogs. Conclusions The present study provides evidence that bradykinin elicits urethral smooth muscle contraction via the bradykinin B2 receptor, suggesting the potential utility of this receptor as a novel target for the treatment of voiding dysfunction.