title: Role of alveolar β2-adrenergic receptors on lung fluid clearance and exercise ventilation in healthy humans.
abstract: BACKGROUND
  In experimental conditions alveolar fluid clearance is controlled by alveolar β2-adrenergic receptors. We hypothesized that if this occurs in humans, then non-selective β-blockers should reduce the membrane diffusing capacity (DM), an index of lung interstitial fluid homeostasis. Moreover, we wondered whether this effect is potentiated by saline solution infusion, an intervention expected to cause interstitial lung edema. Since fluid retention within the lungs might trigger excessive ventilation during exercise, we also hypothesized that after the β2-blockade ventilation increased in excess to CO2 output and this was further enhanced by interstitial edema.
  
  
  RESULTS
  22 healthy males took part in the study. On day 1, spirometry, lung diffusion for carbon monoxide (DLCO) including its subcomponents DM and capillary volume (VCap), and cardiopulmonary exercise test were performed. On day 2, these tests were repeated after rapid 25 ml/kg saline infusion. Then, in random order 11 subjects were assigned to oral treatment with Carvedilol (CARV) and 11 to Bisoprolol (BISOPR). When heart rate fell at least by 10 beats·min(-1), the tests were repeated before (day 3) and after saline infusion (day 4). CARV but not BISOPR, decreased DM (-13 ± 7%, p = 0.001) and increased VCap (+20 ± 22%, p = 0.016) and VE/VCO2 slope (+12 ± 8%, p<0.01). These changes further increased after saline: -18 ± 13% for DM (p<0.01), +44 ± 28% for VCap (p<0.001), and +20 ± 10% for VE/VCO2 slope (p<0.001).
  
  
  CONCLUSIONS
  These findings support the hypothesis that in humans in vivo the β2-alveolar receptors contribute to control alveolar fluid clearance and that interstitial lung fluid may trigger exercise hyperventilation.
authors.affiliation: Centro Cardiologico Monzino, Istituto Di Ricovero e Cura a Carattere Scientifico, Milano, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Paolillo
authors.forename: Riccardo
authors.initials: R
authors.lastname: Pellegrino
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Salvioni
authors.forename: Mauro
authors.initials: M
authors.lastname: Contini
authors.forename: Annamaria
authors.initials: A
authors.lastname: Iorio
authors.forename: Francesca
authors.initials: F
authors.lastname: Bovis
authors.forename: Andrea
authors.initials: A
authors.lastname: Antonelli
authors.forename: Roberto
authors.initials: R
authors.lastname: Torchio
authors.forename: Carlo
authors.initials: C
authors.lastname: Gulotta
authors.forename: Alessandro
authors.initials: A
authors.lastname: Locatelli
authors.forename: Piergiuseppe
authors.initials: P
authors.lastname: Agostoni
mesh_terms: D000328:Adult; D017298:Bisoprolol / Q000627:therapeutic use; D002227:Carbazoles / Q000627:therapeutic use; D000077261:Carvedilol; D015444:Exercise / Q000502:physiology*; D045604:Extracellular Fluid / Q000378:metabolism; D006801:Humans; D006985:Hyperventilation / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D011412:Propanolamines / Q000627:therapeutic use; D011653:Pulmonary Diffusing Capacity / Q000187:drug effects; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism*; D012129:Respiratory Function Tests; D055815:Young Adult
chemical_list: D002227:Carbazoles; D011412:Propanolamines; D018343:Receptors, Adrenergic, beta-2; D000077261:Carvedilol; D017298:Bisoprolol