fr-173657 and Cough

To investigate the effect of bradykinin B(2) receptor antagonist FR173657 on cough response in guinea pigs sensitized and challenged with ovalbumin.. 40 normal and 40 sensitized guinea pigs were challenged with the aerosol of ovalbumin. 24 hours later, 10 animals from the normal group and 10 from the sensitized group were intraperitoneally injected either with saline or with 0.03 mg/kg, 0.3 mg/kg and 3 mg/kg of FR173657 respectively, and then cough response to inhaled capsaicin was measured. Specific airway resistance was recorded with a noninvasive technique only in normal, sensitized and FR173657 (0.3 mg/kg)-treated sensitized guinea pigs.. FR173657 did not influence cough response and airway resistance in normal guinea pigs. Compared with normal animals, sensitized guinea pigs presented an increased cough frequency and specific airway resistance [(21.7 +/- 3.0) times/3 min vs (8.3 +/- 1.4) times/3 min, (9.4 +/- 0.5) cm H(2)O/s vs (7.9 +/- 0.9) cm H(2)O/s], (P < 0.05) after inhalation of 10(-4) mol/L capsaicin. The cough frequency and specific airway resistance were decreased to [(12.2 +/- 1.3) times/1 min and (7.5 +/- 0.9) cm H(2)O/s] after administration of 0.3 mg/kg of FR173657 (P < 0.05).. Bradykinin B(2) receptor antagonist inhibited increased cough response and airway resistance in guinea pigs sensitized and challenged with ovalbumin. Bradykinin may be an important mediator in cough associated with eosinophilic airway inflammation.

Topics: Airway Resistance; Animals; Asthma; Bradykinin Receptor Antagonists; Capsaicin; Cough; Disease Models, Animal; Guinea Pigs; Male; Ovalbumin; Quinolines; Receptor, Bradykinin B2