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 antagonist Hoe 140. The efficacy of Hoe 140 treatment was assessed through its effect on the bradykinin-induced (up to 2.5 microgram/100 g B.W. administered intravenously) decrease in blood pressure (BP). Hoe 140 (0.1 micromol/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 micromol/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.
Folkerts
G
G
Departments of Pharmacology and Pathophysiology, and Medicinal Chemistry, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands. G.Folkerts@pharm.uu.nl
Vlieger
J W
JW
de Vries
A
A
Faas
S
S
van Der Linde
H
H
Engels
F
F
de Jong
J C
JC
Verheyen
F A
FA
Van Heuven-Nolsen
D
D
Nijkamp
F P
FP
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D065168:Bradykinin Receptor Antagonists; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D006168:Guinea Pigs; D008168:Lung / Q000473:pathology; D008297:Male; D010224:Parainfluenza Virus 3, Human; D012141:Respiratory Tract Infections / Q000473:pathology / Q000503:physiopathology*; D010253:Respirovirus Infections / Q000473:pathology / Q000503:physiopathology*
D000319:Adrenergic beta-Antagonists; D065168:Bradykinin Receptor Antagonists; C065679:icatibant; D001920:Bradykinin