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01.12.2014 | Research | Ausgabe 1/2014 Open Access

Respiratory Research 1/2014

The effects of salbutamol on epithelial ion channels depend on the etiology of acute respiratory distress syndrome but not the route of administration

Zeitschrift:
Respiratory Research > Ausgabe 1/2014
Autoren:
Christopher Uhlig, Pedro L Silva, Débora Ornellas, Raquel S Santos, Paulo J Miranda, Peter M Spieth, Thomas Kiss, Michael Kasper, Bärbel Wiedemann, Thea Koch, Marcelo M Morales, Paolo Pelosi, Marcelo Gama de Abreu, Patricia RM Rocco
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1465-9921-15-56) contains supplementary material, which is available to authorized users.
Christopher Uhlig, Pedro L Silva contributed equally to this work.

Competing interests

The authors have no competing interests to declare.
This study was financially supported by a personnel exchange grant (PROBRAL) of the Coordination for the Improvement of Higher Education Personnel (CAPES), Brasília, Brazil, and the German Academic Exchange Service (DAAD), Bonn, Germany, as well as educational grants of the Carlos Chagas Filho Rio de Janeiro State Research Foundation (FAPERJ), Rio de Janeiro, Brazil, and the Brazilian Council for Scientific and Technological Development (CNPq), Brasília, Brazil.

Authors’ contributions

CPU participated in the design of the study, carried out the experiments, performed data analyses and drafted the manuscript; PLS contributed to the study design, carried out the experiments, performed data analyses, and wrote the manuscript; DO carried out the molecular biology analyses and contributed to the manuscript; RSS and PJM provided expert assistance during experiments, analyzed mechanical data, and helped draft the manuscript; PMS and TK contributed to the study design and manuscript; MK performed the histological analyses and helped draft the manuscript; BW performed the statistical analyses and helped draft the manuscript; MMM contributed to study design and carried out the molecular biology analyses; PP contributed to the study design, supervised the entire project and helped write the manuscript; MGA and PRMR: contributed to the study design, supervised the experimental work and statistical analysis, wrote the manuscript, supervised the entire project. All authors read and approved the final manuscript.

Abstract

Introduction

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. SALB.

Results

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.

Conclusion

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.
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