Dopamine Stimulates Sodium Transport and Liquid  Clearance in Rat Lung Epithelium

Barnard, M. L.; Olivera, Walter; Rutschman, David M.; Bertorello, Alejandro M.; Katz, Adriana; Sznajder, Jacob I.

doi:10.1164/ajrccm.156.3.9610013

Cited by 83 publications

(80 citation statements)

References 26 publications

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“…These findings were associated with increases in Na,K-ATPase function in AT2 cells (5). Similar findings have been reported after treatment of alveolar epithelial cells and lungs with dopamine, dobutamine, and isoproterenol (16)(17)(18). These studies show that increased Na,K-ATPase expression is associated with increased Na,K-ATPase function and lung liquid clearance, suggesting that alveolar Na,K-ATPases play an important role in keeping the alveolus free from edema.…”

Section: Introductionsupporting

confidence: 81%

See 1 more Smart Citation

Augmentation of lung liquid clearance via adenovirus-mediated transfer of a Na,K-ATPase beta1 subunit gene.

Saldías¹,

Ridge

Dumasius³

et al. 1998

J. Clin. Invest.

129

131

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Previous studies have suggested that alveolar Na,K-ATPases play an important role in active Na ϩ transport and lung edema clearance. We reasoned that overexpression of Na,K-ATPase subunit genes could increase Na,K-ATPase function in lung epithelial cells and edema clearance in rat lungs. To test this hypothesis we produced replication deficient human type 5 adenoviruses containing cDNAs for the rat ␣ 1 and ␤ 1 Na,K-ATPase subunits (adMRCMV ␣ 1 and adMRCMV ␤ 1 , respectively). As compared to controls, adMRCMV ␤ 1 increased ␤ 1 subunit expression and Na,KATPase function by 2.5-fold in alveolar type 2 epithelial cells and rat airway epithelial cell monolayers. No change in Na,K-ATPase function was noted after infection with adMRCMV ␣ 1 . Rat lungs infected with adMRCMV ␤ 1 , but not adMRCMV ␣ 1 , had increased ␤ 1 protein levels and lung liquid clearance 7 d after tracheal instillation. Alveolar epithelial permeability to Na ϩ and mannitol was mildly increased in animals infected with adMRCMV ␤ 1 and a similar Escherichia coli lacZ -expressing virus. Our data shows, for the first time, that transfer of the ␤ 1 Na,K-ATPase subunit gene augments Na,K-ATPase function in epithelial cells and liquid clearance in rat lungs. Conceivably, overexpression of Na,K-ATPases could be used as a strategy to augment lung liquid clearance in patients with pulmonary edema. (

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Section: Introductionsupporting

confidence: 81%

“…Calculations for isolated-perfused rat model (2,5,(14)(15)(16). Concentration of EBD-albumin was used to estimate airspace volume.…”

Section: Nak-atpase Function In At2 Cells Ouabain-sensitive 86mentioning

confidence: 99%

Augmentation of lung liquid clearance via adenovirus-mediated transfer of a Na,K-ATPase beta1 subunit gene.

Saldías¹,

Ridge

Dumasius³

et al. 1998

J. Clin. Invest.

129

131

View full text Add to dashboard Cite

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“…Although only small increases in net ion transport across FDLE monolayers were observed, explants exhibited 50% less expansion over 24 h after DA treatment, suggesting that DAs effects may be of biologic significance. Our data are consistent with previous findings that DA increases fluid clearance in an isolated lung model (11,26), and activates amiloride-sensitive ion transport in alveolar type I cells (27). Our dose-response studies showed small effects of DA at physiologic doses of DA [10 Ϫ8 M to 10 Ϫ7 M (28)], although the effects were not large enough to reach statistical significance.…”

Section: Discussionsupporting

confidence: 92%

“…They secrete many mediators, including dopamine (DA), serotonin, gastrin-releasing peptide (GRP), and somatostatin, (7)(8)(9) which may play a role in the lungs' transition to postnatal life by altering fetal lung epithelial ion and fluid transport. DA concentrations are maximal at birth (10), and it is known to alter alveolar fluid transport by increasing Na ϩ channel and Na ϩ /K ϩ -ATPase activity (10,11). Some studies suggest that serotonin may have a similar role in fluid clearance in the fetal lung (12); however, others suggest that serotonin decreases transepithelial Na ϩ transport (13).…”

mentioning

confidence: 99%

Pulmonary Neuroendocrine Cell-Secreted Factors May Alter Fetal Lung Liquid Clearance

et al. 2009

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ABSTRACT:The neuroendocrine system is most active at birth and may play a role in the transition from fetal to postnatal life, in particular in the lungs' transition from fluid secretion to fluid absorption. Pulmonary neuroendocrine cells do release dopamine (DA), serotonin, and gastrin-releasing peptide but their effects on lung ion and fluid transport are poorly understood. Therefore, we studied their effects on fetal distal lung explants and primary cultures of fetal distal lung epithelium (FDLE). We show that DA, but neither serotonin nor gastrin-releasing peptide, alters ion and fluid transport, in a dosedependent manner. DAs effects were abrogated by D1/D2 receptor blockers in FDLE but not in explants. Propranolol abrogated DAs effects in both models. DA increased intracellular cAMP levels in FDLE. Terbutaline, forskolin, and isobutylmethylxanthine did not increase short circuit current (Isc) in DA-treated cells, despite a further increase in cAMP. We conclude that at least one, but not all mediators released by pulmonary neuroendocrine cells alter distal lung epithelial ion transport. (Pediatr Res 65: 274-278, 2009)

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“…Low to moderate doses have dopaminergic effects and have been shown to increase alveolar fluid clearance experimentally (3,4,34). Therefore, the primary analysis of dopamine was done on lungs that had been exposed to low to moderate doses of dopamine.…”

Section: Methodsmentioning

confidence: 99%

Selected Contribution: Mechanisms that may stimulate the resolution of alveolar edema in the transplanted human lung

Ware

Fang

Wang

et al. 2002

Journal of Applied Physiology

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nary edema is common in organ donors and lung transplant recipients. Therefore, we assessed the responsiveness of human donor lungs to pharmacological agents that stimulate clearance of alveolar edema. Organ donors whose lungs were rejected for transplantation were studied. After resection, transport (4°C), and rewarming (37°C) of lungs, alveolar fluid clearance was measured with (n ϭ 8 donors) or without (n ϭ 23 donors) ␤-adrenergic stimulation. Terbutaline-stimulated clearance (10 Ϫ4 M) was higher than unstimulated clearance (7.1 Ϯ 1.3 vs. 4.8 Ϯ 2.4%/h, P Ͻ 0.01). Second, we determined whether medications given to the organ donor were associated with the extent of pulmonary edema or the rate of alveolar fluid clearance in the harvested lung. Preharvest administration of dopamine in low to moderate doses was associated with faster alveolar fluid clearance (r ϭ 0.62, P Ͻ 0.01). Preharvest administration of diuretics was associated with lower extravascular lung water-to-dry weight ratios. This study provides the first evidence that a ␤ 2-adrenergic agonist stimulates alveolar fluid clearance in the human donor lung. Aerosolized ␤ 2-adrenergic agonists may have therapeutic value for hastening the resolution of alveolar edema during the management of donors before resection of lungs for transplantation or in the posttransplant setting. pulmonary edema; ␤-agonist; alveolar epithelial fluid transport; alveolar epithelium; lung preservation PULMONARY EDEMA IS A COMMON problem in both organ donors and lung transplant recipients. In organ do-

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Dopamine Stimulates Sodium Transport and Liquid Clearance in Rat Lung Epithelium

Cited by 83 publications

References 26 publications

Augmentation of lung liquid clearance via adenovirus-mediated transfer of a Na,K-ATPase beta1 subunit gene.

Augmentation of lung liquid clearance via adenovirus-mediated transfer of a Na,K-ATPase beta1 subunit gene.

Pulmonary Neuroendocrine Cell-Secreted Factors May Alter Fetal Lung Liquid Clearance

Selected Contribution: Mechanisms that may stimulate the resolution of alveolar edema in the transplanted human lung

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