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Effect of atropine on the hyperresponsiveness of ragweed-sensitized canine tracheal smooth muscle

RW Mitchell, LA Antonissen, W Kepron, EA Kroeger and NL Stephens

The present studies were undertaken to obtain histamine (HIST) dose- response curves for tracheal smooth muscle (TSM) from an actively ragweed-sensitized canine model of asthma and to compare these results with 1) HIST dose-response data from littermate control dogs, 2) initially nonsensitized TSM passively sensitized (in vitro) to ragweed and 3) the dose-response curve to an agonist that opens primarily voltage-sensitive calcium channels, i.e., K+. Actively ragweed- sensitized TSM was significantly hyperreactive (upward shift of the dose-response curve) to HIST (1.882 kg of force produced normalized to cross-sectional area-kg/cm2 +/- 0.087 S.E. vs. littermate controls 1.151 +/- 0.253) and hypersensitive as indicated by the leftward shift in the median effective dose or ED50 (1.86 X 10(-6) +/- 0.24 vs. 5.54 X 10(-6) +/- 1.35 M). Passively sensitized TSM (using serum from ragweed- sensitized dogs) also showed a hyperreactivity to HIST when compared to control TSM incubated with control serum (1.204 +/- 0.127 vs. 0.825 +/- 0.081 kg/cm2). No significant difference was found in the ED50 values, indicating similar sensitivities. Atropine (10(-7) M) reduced the hypersensitivity of actively sensitized TSM significantly toward control values; however, the hyperreactivity persisted. Atropine did not affect responses to HIST in control TSM. Ragweed actively sensitized TSMs were also hyperreactive and hypersensitive to K+ when compared to littermate control TSM. Atropine abolished both the hyperreactivity and hypersensitivity to K+ but had no effect on the dose-response curve of control TSM to K+.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 236, Issue 3, pp. 803-809, 03/01/1986
Copyright © 1986 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1986 by the American Society for Pharmacology and Experimental Therapeutics.