Am. J. Respir. Crit. Care Med.,
Volume 161, Number 5, May 2000, 1666-1671
Virus- and Bradykinin-Induced Airway
Hyperresponsiveness in Guinea Pigs
GERT
FOLKERTS,
JANNEKE WESTRA-de
VLIEGER,
ANNICK
de VRIES,
STEPHAN
FAAS,
HENK
van der LINDE,
FERDI
ENGELS,
JAN C.
de JONG,
FONS A. K. C. P.
VERHEYEN,
DICKY
VAN HEUVEN-NOLSEN,
and
FRANS P.
NIJKAMP
Departments of Pharmacology and Pathophysiology, and Medicinal Chemistry, Utrecht Institute for Pharmaceutical Sciences, Utrecht University,
Utrecht; Department of Virology, Faculty of Medicine, Erasmus University Rotterdam, Rotterdam, The Netherlands; and Department of
Cardiovascular and Pulmonary Pharmacology, Janssen Research Foundation, Beerse, Belgium
The involvement of bradykinin in virus-induced airway hyperresponsiveness (AHR) in guinea pig airways in vivo was determined with the B2-receptor antagonist Hoe 140. The efficacy of Hoe 140 treatment was assessed through its effect on the bradykinin-induced (up to 2.5 µg/100 g B.W. administered intravenously) decrease in
blood pressure (BP). Hoe 140 (0.1 µmol/kg), administered subcutaneously twice a day for 5 d almost completely blocked bradykinin-induced changes in BP. Four days after parainfluenza-3 (PI-3)
virus infection, guinea pigs showed AHR; excessive airway contraction was found with histamine-receptor stimulation. This hyperresponsiveness was completely inhibited by pretreatment with Hoe
140 (0.1 µmol/kg) administered subcutaneously twice a day for
five consecutive days, starting 1 d before virus inoculation. Interestingly, nebulized delivery of bradykinin itself to captopril-treated animals induced an AHR comparable to that observed in
virus-treated guinea pigs. Viral infection also caused influx of
bronchoalveolar cells into the lungs. Both histologic examinations
and lung lavage experiments 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 involved in a cascade of
events leading to AHR after a viral infection in guinea pigs, without affecting bronchoalveolar cell influx.
