Sympathetic nerve-dependent regulation of mucosal vascular tone modifies airway smooth muscle reactivity

Stuart B. Mazzone, Lina H.K. Lim, Elizabeth M. Wagner, Nanako Mori, Brendan J. Canning

Research output: Contribution to journalArticle

Abstract

The airways contain a dense subepithelial microvascular plexus that is involved in the supply and clearance of substances to and from the airway wall. We set out to test the hypothesis that airway smooth muscle reactivity to bronchoconstricting agents may be dependent on airway mucosal blood flow. Immunohistochemical staining identified vasoconstrictor and vasodilator nerve fibers associated with subepithelial blood vessels in the guinea pig airways. Intravital microscopy of the tracheal mucosal microvasculature in anesthetized guinea pigs revealed that blockade of α-adrenergic receptors increased baseline arteriole diameter by ∼40%, whereas the α-adrenergic receptor agonist phenylephrine produced a modest (5%) vasoconstriction in excess of the baseline tone. In subsequent in vivo experiments, tracheal contractions evoked by topically applied histamine were significantly reduced (P <0.05) and enhanced by α-adrenergic receptor blockade and activation, respectively. α-Adrenergic ligands produced similar significant (P <0.05) effects on airway smooth muscle contractions evoked by topically administered capsaicin, intravenously administered neurokinin A, inhaled histamine, and topically administered antigen in sensitized animals. These responses were independent of any direct effect of α-adrenergic ligands on the airway smooth muscle tone. The data suggest that changes in blood flow in the vessels supplying the airways regulate the reactivity of the underlying airway smooth muscle to locally released and exogenously administered agents by regulating their clearance. We speculate that changes in mucosal vascular function or changes in neuronal regulation of the airway vasculature may contribute to airways responsiveness in disease.

Original languageEnglish (US)
Pages (from-to)1292-1300
Number of pages9
JournalJournal of applied physiology
Volume109
Issue number5
DOIs
StatePublished - Nov 1 2010

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Keywords

  • Bronchoconstriction
  • Intravital microscopy
  • Particle clearance
  • Tracheobronchial vasculature

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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