Relaxation of activated airway smooth muscle: Relative potency of isoproterenol vs. tidal stretch

Alison Gump, Laura Haughney, Jeffrey Fredberg

Research output: Contribution to journalArticlepeer-review

Abstract

Both isoproterenol and tidal fluctuations of muscle length inhibit active force development in activated airway smooth muscle. In this study, we show that length fluctuations in the range of amplitudes expected during quiet tidal breathing produce force inhibition that is equipotent with high concentrations of isoproterenol. Active force fell to 50% of its isometric value when the amplitude of the tidal stretch was 4% of muscle length. The relaxing effects of length fluctuations were insensitive to the specific contractile agonist, suggesting that the mechanism of action is largely independent of the particular signal transduction pathway and lies instead at the level of bridge dynamics. This idea is reinforced by the results of combining the relaxation effects of tidal fluctuations with those produced by isoproterenol at all but the highest concentrations studied (10-5 M). Such a combination produces multiplicative effects, indicating largely separate modes of action. These observations suggest that the tidal muscle stretches that are attendant to spontaneous breathing comprise the first line of defense against bronchospasm and that tidal muscle stretches may be the most important of all known bronchodilating agencies.

Original languageEnglish (US)
Pages (from-to)2306-2310
Number of pages5
JournalJournal of applied physiology
Volume90
Issue number6
DOIs
StatePublished - Jun 2001
Externally publishedYes

Keywords

  • Bronchodilating agents
  • Bronchospasm
  • β-agonists

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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