title: Role of sensory neuropeptides in PIV-3-infection-induced airway hyperresponsiveness in guinea pigs.
abstract: Viral respiratory tract infections are known to induce transient airway hyper-responsiveness. The role of the nonadrenergic noncholinergic neuropeptide system on virus-induced airway hyperresponsiveness was studied in the guinea pig. Ten guinea pigs were inoculated with parainfluenza 3 virus (PIV-3.2 x 10(6) PFU) by nasal route. 16 animals served as untreated controls. Viral infection was proven by histological changes and by demonstration of viral antigen using immunohistochemical techniques. Four days after inoculation, airway responsiveness to inhaled acetylcholine (ACH) aerosol was measured in anesthetized and tracheotomized guinea pigs. The ACH concentration which produced an increase of 100% in pulmonary resistance (PC100 RI) and in dynamic elastance (PC100 Edyn) was calculated from a 5-step ACH dose-response curve (0.125, 0.25, 0.5, 1.0 and 2.0% ACH). Two further groups of 8 PIV-3-infected guinea pigs and 8 noninfected control animals were pretreated with capsaicin in increasing doses (50, 100, 125 and 150 mg/kg) on 4 consecutive days starting 6 days before virus inoculation. Measurements of airway responsiveness to ACH were performed 4 days after virus inoculation. Another 5 uninfected control animals were pretreated only with the solvent for capsaicin and inoculated with virus-free cell supermatant. PIV-3 infection increased airway responsiveness to ACH compared to noninfected controls [PC100 RI 0.81 vs. > 2.0% ACH (median). p < 0.002 PC100 Edyn 0.52 vs. 1.07% ACH (median), p < 0.01]. In capsaicin-pretreated PIV-3-infected animals, airway hyperresponsiveness was completely prevented compared to the virus-infected group without capsaicin pretreatment (PC100 RI > 2.0 vs. 0.81% ACH, p < 0.01; PC100 Edyn 1.42 vs. 0.52% ACH p < 0.01). As neuropeptide depletion with capsaicin completely prevented the increase in airway constrictory response to ACH following virus infection, we conclude that neuropeptides are effectively involved in PIV-3-induced airway hyperresponsiveness in the guinea pig.
authors.affiliation: Department of Pediatrics, Ruhr University Bochum, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Riedel
authors.forename: C
authors.initials: C
authors.lastname: Benden
authors.forename: S
authors.initials: S
authors.lastname: Philippou
authors.forename: H J
authors.initials: HJ
authors.lastname: Streckert
authors.forename: W
authors.initials: W
authors.lastname: Marek
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000502:physiology*; D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D001985:Bronchial Provocation Tests; D002211:Capsaicin / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D008168:Lung / Q000473:pathology; D008853:Microscopy; D009479:Neuropeptides / Q000096:biosynthesis / Q000187:drug effects; D010224:Parainfluenza Virus 3, Human / Q000472:pathogenicity*; D012016:Reference Values; D012130:Respiratory Hypersensitivity / Q000473:pathology / Q000503:physiopathology* / Q000821:virology; D010253:Respirovirus Infections / Q000503:physiopathology*
chemical_list: D009479:Neuropeptides; D000109:Acetylcholine; D002211:Capsaicin