title: beta-adrenergic stimulation restores rat lung ability to clear edema in ventilator-associated lung injury.
abstract: Mechanical ventilation with high tidal volume (HVT) causes lung injury and decreases the lung's ability to clear edema in rats. beta-adrenergic agonists increase active Na(+) transport and lung edema clearance in normal rat lungs by stimulating apical Na(+) channels and basolateral Na,K-ATPase in alveolar epithelial cells. We studied whether beta-adrenergic agonists could restore lung edema clearance in rats ventilated with HVT (40 ml/kg, peak airway pressure of 35 cm H(2)O) for 40 min. The ability of rat lungs to clear edema decreased by approximately 50% after 40 min of HVT ventilation. Terbutaline (TERB) and isoproterenol (ISO) increased lung edema clearance in control nonventilated rats (from 0.50 +/- 0. 02 ml/h to 0.81 +/- 0.04 ml/h and 0.99 +/- 0.05 ml/h, respectively) and restored the lung's ability to clear edema in HVT ventilated rats (from 0.25 +/- 0.03 ml/h to 0.64 +/- 0.02 ml/h and 0.88 +/- 0. 09 ml/h, respectively). Disruption of cell microtubular transport system by colchicine inhibited the stimulatory effects of ISO in HVT ventilated rats, whereas beta-lumicolchicine did not affect beta-adrenergic stimulation. The Na,K-ATPase alpha(1)- and beta(1)-subunit mRNA steady state levels were not affected by incubation with ISO for 60 min in alveolar type II cells isolated from control and HVT ventilated rats. The data suggest that beta-adrenergic agonists increased alveolar fluid reabsorption in rats ventilated with HVT by promoting recruitment of ion-transporting proteins from intracellular pools to the plasma membrane of alveolar epithelial cells.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Northwestern University Medical School, and Northeastern University, Chicago, Illinois 60611, USA.
authors.forename: F J
authors.initials: FJ
authors.lastname: Saldías
authors.forename: E
authors.initials: E
authors.lastname: Lecuona
authors.forename: A P
authors.initials: AP
authors.lastname: Comellas
authors.forename: K M
authors.initials: KM
authors.lastname: Ridge
authors.forename: D H
authors.initials: DH
authors.lastname: Rutschman
authors.forename: J I
authors.initials: JI
authors.lastname: Sznajder
mesh_terms: D000318:Adrenergic beta-Agonists / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D007545:Isoproterenol / Q000493:pharmacokinetics / Q000627:therapeutic use*; D055370:Lung Injury; D008297:Male; D010539:Permeability; D011654:Pulmonary Edema / Q000188:drug therapy* / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects*; D020545:Respiratory Mucosa / Q000378:metabolism; D013726:Terbutaline / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000318:Adrenergic beta-Agonists; D007545:Isoproterenol; D013726:Terbutaline