Comparison of drug responses in vivo and in vitro in airways of dogs with and without airway hyperresponsiveness

H Downes, DR Austin, CM Parks and CA Hirshman

Basenji-greyhound (BG) dogs demonstrate marked nonspecific airway hyperresponsiveness. To assess the possible contribution of an abnormal sensitivity of airway smooth muscle to this phenomenon, we studied the in vitro contractile responses to methacholine and histamine and the relaxant response to isoproterenol in trachealis muscle from five BG dogs with airway hyperresponsiveness in vivo and from five greyhound dogs that served as a control population. Isoproterenol responses were determined against a half-maximal methacholine contraction. Aerosol methacholine concentrations required to produce a 2-fold increase in pulmonary resistance were 0.07 +/- 0.02 (+/- S.E.) mg/ml in BG dogs and 0.67 +/- 0.26 mg/ml in greyhounds; pD2 values for methacholine-induced contraction of cervical trachealis muscle were 7.03 +/- 0.11 in BG dogs and 7.50 +/- 0.11 in greyhounds. A significant (P less than .01) negative correlation was found between methacholine sensitivity in vivo and in vitro. Aerosol concentrations of histamine required to produce a 2-fold increase in pulmonary resistance were 0.19 +/- 0.06 mg/ml in BG dogs and 1.44 +/- 0.43 mg/ml in greyhounds; pD2 values for histamine were identical in BG dogs (4.95 +/- 0.08) and greyhounds (5.05 +/- 0.19). Isoproterenol pD2 values were less in the trachealis muscle (cervical) of BG dogs (6.76 +/- 0.10) than in that of greyhounds (7.93 +/- 0.16), but this is probably a consequence of the higher concentration of methacholine needed to contract BG muscles. We conclude that the airway hyperresponsiveness of BG dogs does not reflect an increased sensitivity of airway smooth muscle per se.

Volume 237, Issue 1, pp. 214-219, 04/01/1986
Copyright © 1986 by American Society for Pharmacology and Experimental Therapeutics

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