title: The effects of salbutamol on epithelial ion channels depend on the etiology of acute respiratory distress syndrome but not the route of administration.
abstract: BACKGROUND
  We investigated the effects of intravenous and intratracheal administration of salbutamol on lung morphology and function, expression of ion channels, aquaporin, and markers of inflammation, apoptosis, and alveolar epithelial/endothelial cell damage in experimental pulmonary (p) and extrapulmonary (exp) mild acute respiratory distress syndrome (ARDS).
  
  
  METHODS
  In this prospective randomized controlled experimental study, 56 male Wistar rats were randomly assigned to mild ARDS induced by either intratracheal (n = 28, ARDSp) or intraperitoneal (n = 28, ARDSexp) administration of E. coli lipopolysaccharide. Four animals with no lung injury served as controls (NI). After 24 hours, animals were anesthetized, mechanically ventilated in pressure-controlled mode with low tidal volume (6 mL/kg), and randomly assigned to receive salbutamol (SALB) or saline 0.9% (CTRL), intravenously (i.v., 10 μg/kg/h) or intratracheally (bolus, 25 μg). Salbutamol doses were targeted at an increase of ≈ 20% in heart rate. Hemodynamics, lung mechanics, and arterial blood gases were measured before and after (at 30 and 60 min) salbutamol administration. At the end of the experiment, lungs were extracted for analysis of lung histology and molecular biology analysis. Values are expressed as mean ± standard deviation, and fold changes relative to NI, CTRL vs.
  The gene expression of ion channels and aquaporin was increased in mild ARDSp, but not ARDSexp. In ARDSp, intravenous salbutamol resulted in higher gene expression of alveolar epithelial sodium channel (0.20 ± 0.07 vs. 0.68 ± 0.24, p < 0.001), aquaporin-1 (0.44 ± 0.09 vs. 0.96 ± 0.12, p < 0.001) aquaporin-3 (0.31 ± 0.12 vs. 0.93 ± 0.20, p < 0.001), and Na-K-ATPase-α (0.39 ± 0.08 vs. 0.92 ± 0.12, p < 0.001), whereas intratracheal salbutamol increased the gene expression of aquaporin-1 (0.46 ± 0.11 vs. 0.92 ± 0.06, p < 0.001) and Na-K-ATPase-α (0.32 ± 0.07 vs. 0.58 ± 0.15, p < 0.001). In ARDSexp, the gene expression of ion channels and aquaporin was not influenced by salbutamol. Morphological and functional variables and edema formation were not affected by salbutamol in any of the ARDS groups, regardless of the route of administration.
  
  
  CONCLUSIONS
  Salbutamol administration increased the expression of alveolar epithelial ion channels and aquaporin in mild ARDSp, but not ARDSexp, with no effects on lung morphology and function or edema formation. These results may contribute to explain the negative effects of β2-agonists on clinical outcome in ARDS.
authors.forename: Christopher
authors.initials: C
authors.lastname: Uhlig
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Silva
authors.forename: Débora
authors.initials: D
authors.lastname: Ornellas
authors.forename: Raquel S
authors.initials: RS
authors.lastname: Santos
authors.forename: Paulo J
authors.initials: PJ
authors.lastname: Miranda
authors.forename: Peter M
authors.initials: PM
authors.lastname: Spieth
authors.forename: Thomas
authors.initials: T
authors.lastname: Kiss
authors.forename: Michael
authors.initials: M
authors.lastname: Kasper
authors.forename: Bärbel
authors.initials: B
authors.lastname: Wiedemann
authors.forename: Thea
authors.initials: T
authors.lastname: Koch
authors.forename: Marcelo M
authors.initials: MM
authors.lastname: Morales
authors.forename: Paolo
authors.initials: P
authors.lastname: Pelosi
authors.affiliation: Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Av, Carlos Chagas Filho s/n, Bloco G-014, Rio de Janeiro, RJ 21941-902, Brazil. mgabreu@uniklinikum-dresden.de.
authors.forename: Marcelo Gama
authors.initials: MG
authors.lastname: de Abreu
authors.forename: Patricia Rm
authors.initials: PR
authors.lastname: Rocco
mesh_terms: D061605:Administration, Intravenous; D000420:Albuterol / Q000008:administration & dosage*; D000818:Animals; D007278:Injections, Spinal; D007473:Ion Channels / Q000096:biosynthesis*; D008297:Male; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D007473:Ion Channels; D000420:Albuterol