Virus- and bradykinin-induced airway hyperresponsiveness in guinea pigs

The involvement of bradykinin in virus-induced airway hyperresponsiveness ( AHR) in guinea pig airways in vivo was determined with the B-2-receptor ant agonist Hoe 140. The efficacy of Hoe 140 treatment was assessed through its effect on the bradykinin-induced (up to 2.5 mu g/100 g B.W. administered i ntravenously) decrease in blood pressure (BP). Hoe 140 (0.1 mu mol/kg), adm inistered subcutaneously twice a day for 5 d almost completely blocked brad ykinin-induced changes in BP. Four days after parainfluenza-3 (PI-3) virus infection, guinea pigs showed AHR; excessive airway contraction was found w ith histamine-receptor stimulation. This hyperresponsiveness was completely inhibited by pretreatment with Hoe 140 (0.1 mu mol/kg) administered subcut aneously twice a day for five consecutive days, starting 1 d before virus i noculation. Interestingly, nebulized delivery of bradykinin itself to capto pril-treated animals induced an AHR comparable to that observed in virus-tr eated guinea pigs. Viral infection also caused influx of bronchoalveolar ce lls into the lungs. Both histologic: examinations and lung lavage experimen ts showed that this cell influx could not be inhibited by pretreatment with Hoe 140. In summary, the results of the study show that bradykinin is invo lved in a cascade of events leading to AHR after a viral infection in guine a pigs, without affecting bronchoalveolar cell influx.