Potentiation by viral respiratory infection of ovalbumin-induced guinea-pig tracheal hyperresponsiveness: role for tachykinins.
1. We investigated whether virus-induced airway hyperresponsiveness in guinea-pigs could be modulated by pretreatment with capsaicin and whether viral respiratory infections could potentiate ovalbumin-aerosol-induced tracheal hyperresponsiveness. 2. Animals were inoculated intratracheally with bovine parainfluenza-3 virus or control medium 7 days after treatment with capsaicin (50 mg kg-1, s.c.). Four days after inoculation, tracheal contractions were measured to increasing concentrations of substance P, histamine and the cholinoceptor agonist, arecoline. 3. In tracheae from virus-infected guinea-pigs, contractions in response to substance P, histamine and arecoline were significantly enhanced (P < 0.01) by 144%, 46% and 77%, respectively. Capsaicin pretreatment inhibited the hyperresponsiveness to substance P partly (62%) and to histamine and arecoline completely. 4. In another series of experiments animals were first sensitized with ovalbumin (20 mg kg-1, i.p.). After 14 days animals were exposed to either saline or ovalbumin aerosols for 8 days. After 4 aerosol exposures (4 days) animals were inoculated with either parainfluenza-3 virus or control medium. One day after the last ovalbumin aerosol, tracheal contraction in response to increasing concentrations of substance P, histamine and arecoline was measured. 5. Tracheae from ovalbumin-aerosol-exposed control inoculated animals showed a similar degree of airway hyperresponsiveness to saline-aerosol-exposed virus-treated guinea-pigs. Virus inoculation of ovalbumin-treated animals significantly potentiated the tracheal contractions to substance P compared to either of the treatments alone. The contractions in response to histamine and arecoline were only slightly enhanced. 6. In conclusion, sensory nerves and/or tachykinins are involved in virus-induced airway hyperresponsivenessin guinea-pigs and viral respiratory infections can potentiate the increase in tracheal responsiveness to bronchoconstrictor agonists after ovalbumin exposure.
Ladenius
A R
AR
Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands.
Folkerts
G
G
van der Linde
H J
HJ
Nijkamp
F P
FP
D000818:Animals; D001115:Arecoline / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006967:Hypersensitivity; D008297:Male; D010047:Ovalbumin / Q000494:pharmacology*; D012141:Respiratory Tract Infections / Q000139:chemically induced*; D013373:Substance P / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects*; D014776:Virus Cultivation
D015320:Tachykinins; D013373:Substance P; D001115:Arecoline; D006632:Histamine; D010047:Ovalbumin; D002211:Capsaicin