Effect of β3-adrenergic agonists on alveolar fluid clearance in hypoxic rat lungs

Background Recent research suggests that β2-adrenergic agonists increase alveolar fluid clearance （AFC） under physiologic and pathologic conditions. It is unknown whether β3-adrenergic agonists also increase AFC under pathologic conditions. The aim of this study was to investigate the effect of β3-adrenergic agonists on AFC following hypoxic lung injury and the mechanisms involved. Methods Hypoxic rats were exposed to 10% oxygen. BRL-37344 （133-adrenergic agonist） or CGP-12177 （selective β3-adrenergic agonist） alone or combined with β receptor antagonists, sodium channel blockers, or Na＋/＋^-ATPase blockers were perfused into the alveolar space of rats exposed to 10% oxygen for 48 hours. Total lung water content （TLW） and AFC were measured. Results AFC did not change for the first 24 hours but then decreased after 48-hour exposure to 10% oxygen. The perfusion of BRL-37344 or CGP-12177 significantly increased AFC in normal and hypoxic rats. The AFC-stimulating effect of CGP-12177 was lowered with amiloride （a Na＋ channel blocker） and ouabain （a Na~/K^-ATPase inhibitor） by 37% and 49%, respectively. Colchicine significantly inhibited the effect of CGP-12177. Conclusions These findings suggest that β3-adrenergic agonists can increase AFC during hypoxic lung injury in rats and accelerate the amelioration of pulmonary edema.

Specialized Pro-resolving Mediators Regulate Alveolar Fluid Clearance during Acute Respiratory Distress Syndrome

Objective：Acute respiratory distress syndrome （ARDS） is an acute and lethal clinical syndrome that is characterized by the injury of alveolar epithelium, which impairs active fluid transport in the lung, and impedes the reabsorption of edema fluid from the alveolar space. This review aimed to discuss the role of pro-resolving mediators on the regulation of alveolar fluid clearance （AFC） in ARDS.Data Sources：Articles published up to September 2017 were selected from the PubMed, with the keywords of ＂alveolar fluid clearance＂ or ＂lung edema＂ or ＂acute lung injury＂ or ＂acute respiratory distress syndrome＂ , and ＂specialized pro-resolving mediators＂ or ＂lipoxin＂ or ＂resolvin＂ or ＂protectin＂ or ＂maresin＂ or ＂alveolar epithelial cells＂ or ＂aspirin-triggered lipid mediators＂ or ＂carbon monoxide and heme oxygenase＂ or ＂annexin A1＂ .Study Selection：We included all relevant articles published up to September 2017, with no limitation of study design.Results：Specialized pro-resolving mediators （SPMs）, as the proinflammatory mediators, not only upregulated epithelial sodium channel, Na,K-ATPase, cystic fibrosis transmembrane conductance regulator （CFTR）, and aquaporins levels, but also improved Na,K-ATPase activity to promote AFC in ARDS. In addition to the direct effects on ion channels and pumps of the alveolar epithelium, the SPMs also inhibited the inflammatory cytokine expression and improved the alveolar epithelial cell repair to enhance the AFC in ARDS.Conclusions：The present review discusses a novel mechanism for pulmonary edema fluid reabsorption. SPMs might provide new opportunities to design ＂reabsorption-targeted＂ therapies with high degrees of precision in controlling ALI/ARDS.