Comparison of in vitro drug responses in airways of atopic dogs with and without in vivo airway hyperresponsiveness.
For comparison with previous studies in greyhounds and in the Basenji-Greyhound dog model of asthma (BG), basenji dogs were studied under identical conditions with respect to airway responsiveness to inhaled methacholine, cutaneous responses to intradermal antigen injection, and the sensitivity of isolated trachealis muscle to methacholine and isoproterenol. The relaxant effect of isoproterenol was assessed in trachealis muscle precontracted with methacholine (ED50). The basenji dogs resembled the BG dogs in that they showed multiple positive skin tests. Further, trachealis muscle showed a markedly reduced sensitivity to methacholine (pD2 6.64 +/- 0.10) (+/- S.E.) in vitro. However, basenji dogs resembled the greyhounds in requiring high concentrations of methacholine aerosols to produce a 2-fold increase in pulmonary resistance (1.68 mg/ml +/- 1.21). Thus, there were no significant correlations between sensitivity to methacholine in vitro and airway responsiveness to methacholine in vivo; however, the reduced sensitivity to methacholine in vitro in both basenji and BG dogs may be related to the marked atopy characteristic of both groups. In vitro sensitivity to isoproterenol was correlated (r = 0.82) with the concentration of methacholine needed to elicit the test contraction, but isoproterenol sensitivity in BG dogs was significantly less (p = .0027) than that predicted by the common regression line. This deficit in beta adrenergic function in trachealis muscle unrelated to atopy may be important in the in vivo airway hyperresponsiveness of BG dogs.
Downes
H
H
Department of Pharmacology, Oregon Health Sciences University, Portland 97201.
Austin
D R
DR
Parks
C M
CM
Hirshman
C A
CA
D000336:Aerosols; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D004285:Dogs; D006969:Hypersensitivity, Immediate / Q000503:physiopathology*; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology; D008688:Methacholine Compounds / Q000008:administration & dosage / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D015656:Respiratory Mechanics / Q000187:drug effects; D012137:Respiratory System / Q000187:drug effects / Q000503:physiopathology*; D012882:Skin Tests; D014132:Trachea / Q000187:drug effects
D000336:Aerosols; D008688:Methacholine Compounds; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol