Effect of airway acidosis and alkalosis on airway vascular smooth muscle responsiveness to albuterol

Jose E. Cancado, Eliana S. Mendes, Johana Arana, Gabor Horvath, Maria E. Monzon, Matthias Salathe, Adam Wanner

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Background: In vitro and animal experiments have shown that the transport and signaling of β2-adrenergic agonists are pH-sensitive. Inhaled albuterol, a hydrophilic β2-adrenergic agonist, is widely used for the treatment of obstructive airway diseases. Acute exacerbations of obstructive airway diseases can be associated with changes in ventilation leading to either respiratory acidosis or alkalosis thereby affecting albuterol responsiveness in the airway. The purpose of this study was to determine if airway pH has an effect on albuterol-induced vasodilation in the airway. Methods: Ten healthy volunteers performed the following respiratory maneuvers: quiet breathing, hypocapnic hyperventilation, hypercapnic hyperventilation, and eucapnic hyperventilation (to dissociate the effect of pH from the effect of ventilation). During these breathing maneuvers, exhaled breath condensate (EBC) pH and airway blood flow response to inhaled albuterol (δQaw) were assessed. Results: Mean±SE EBC pH (units) and δQaw (μl.min-1.mL-1) were 6.4±0.1 and 16.8±1.9 during quiet breathing, 6.3±0.1 and 14.5±2.4 during eucapnic hyperventilation, 6.6±0.2 and -0.2±1.8 during hypocapnic hyperventilation (p=0.02 and <0.01 vs. quiet breathing), and 5.9±0.1 and 2.0±1.5 during hypercapnic hyperventilation (p=0.02 and <0.02 vs quiet breathing). Conclusions: Albuterol responsiveness in the airway as assessed by δQaw is pH sensitive. The breathing maneuver associated with decreased and increased EBC pH both resulted in a decreased responsiveness independent of the level of ventilation. These findings suggest an attenuated response to hydrophilic β2-adrenergic agonists during airway disease exacerbations associated with changes in pH.

Original languageEnglish (US)
Article number9
JournalBMC Pharmacology and Toxicology
Issue number1
StatePublished - Apr 2 2015


  • Airway blood flow
  • Airway surface liquid pH
  • Albuterol
  • Respiratory acidosis
  • Respiratory alkalosis

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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