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Transepithelial sodium and water transport in the lung

Major player and novel therapeutic target in pulmonary edema

  • Chapter
Hypoxia

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 502))

Abstract

Active transepithelial transport of sodium from the airspaces to the lung interstitium is a primary mechanism driving alveolar fluid clearance. This mechanism depends on sodium uptake by amiloride-sensitive sodium channels on the apical membrane of alveolar type II cells followed by extrusion of sodium on the basolateral surface by the Na-K-ATPase. Injury to the alveolar epithelium can disrupt the integrity of the alveolar barrier or downregulate ion transport pathways thus reducing net alveolar fluid reabsorption, and enhancing the extent of alveolar edema. Endogenous catecholamines upregulate alveolar fluid clearance in several experimental models of acute lung injury, but this upregulation is short-term and often not sufficient to counterbalance alveolar flooding. There is new evidence, however, that pharmacological treatment with beta-adrenergic agonists and/or epithelial growth factors may induce a more sustained stimulation of alveolar fluid reabsorption and in turn facilitate recovery from experimental pulmonary edema. Similar results have been achieved experimentally by gene transfer enhancing the abundance of sodium transporters in the alveolar epithelium. Clinical studies show that impaired alveolar fluid transport mechanisms contribute to the development, severity and outcome of pulmonary edema in humans. Very recent data suggest that mechanisms that augment transepithelial sodium transport and enhance the clearance of alveolar edema may lead to more effective prevention or treatment for pulmonary edema and acute lung injury.

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References

  1. Atabai K, Ware LB, Snider M, Koch P, Daniel B, Nuckton T, and Matthay MA. Aerosolized beta2-agonists achive therapeutic levels in the pulmonary edema fluid of ventilated patients. Am J Resp Crit Care Med 163: A618, 2001.

    Google Scholar 

  2. Azzam ZS, Ridge KM, Factor P, Dumasius V, Rutschman DM, Saldias F, and Sznajder JI. Adenoviral mediated overexpression of the Na-K-ATPase alpha 2 isoform increases alveolar fluid reabsorption in rats. Am J Respir Crit Care Med 161: A286, 2000.

    Google Scholar 

  3. Bachofen M and Weibel ER. Alterations of the gas exchange apparatus in adult respiratory insufficiency associated with septicemia. Am Rev Respir Dis 116: 589–615, 1977.

    PubMed  CAS  Google Scholar 

  4. Bai C, Fukuda N, Song Y, Ma T, Matthay MA, and Verkman AS. Lung fluid transport in aquaporin-1 and aquaporin-4 knockout mice. J Clin Invest 103: 555–561, 1999.

    Article  PubMed  CAS  Google Scholar 

  5. Ballard ST, Schepens SM, Falcone JC, Meininger GA, and Taylor AE. Regional bioelectric properties of porcine airway epithelium. J Appl Physiol 73: 2021–2027, 1992.

    PubMed  CAS  Google Scholar 

  6. Barazzone C, Donati YR, Rochat AF, Vesin C, Kan CD, Pache JC, and Piguet PF. Keratinocyte growth factor protects alveolar epithelium and endothelium from oxygen-induced injury in mice. Am J Pathol 154: 1479–1487, 1999.

    Article  PubMed  CAS  Google Scholar 

  7. Barker PM, Gowen CW, Lawson EE, and Knowles MR. Decreased sodium ion transport across nasal epithelium of very premature infants with respiratory distress syndrome. J Pediatr 130: 373–377, 1997.

    Article  PubMed  CAS  Google Scholar 

  8. Barker PM, Walters DV, Markiewicz M, and Strang LB. Development of the lung liquid reabsorptive mechanism in fetal sheep: synergism of triiodothyronine and hydrocortisone. J Physiol (Lond) 433: 435–449, 1991.

    CAS  Google Scholar 

  9. Barnard ML, Olivera WG, Rutschman DM, Bertorello AM, Katz AI, and Sznajder JI. Dopamine stimulates sodium transport and liquid clearance in rat lung epithelium. Am J Respir Crit Care Med 156: 709–714, 1997.

    PubMed  CAS  Google Scholar 

  10. Berthiaume Y, Broaddus VC, Gropper MA, Tanita T, and Matthay MA. Alveolar liquid and protein clearance from normal dog lungs. J Appl Physiol 65: 585–593, 1988.

    PubMed  CAS  Google Scholar 

  11. Berthiaume Y, Staub NC, and Matthay MA. Beta-adrenergic agonists increase lung liquid clearance in anesthetized sheep. J Clin Invest 79: 335–343, 1987.

    Article  PubMed  CAS  Google Scholar 

  12. Bertorello AM, Ridge KM, Chibalin AV, Katz AI, and Sznajder JI. Isoproterenol increases Na+-K+-ATPase activity by membrane insertion of alpha-subunits in lung alveolar cells. Am J Physiol 276: L20–L27, 1999.

    PubMed  CAS  Google Scholar 

  13. Birnkrant DJ, Mader SL, Van Lunteren E, and Davis PB. Chronic hypoxia increases beta- adrenergic receptor density in the lungs of young and old rats. Mech Ageing Dev 60: 135–142, 1991.

    Article  PubMed  CAS  Google Scholar 

  14. Borok Z, Foster MJ, Zabski SM, Veeraraghavan S, Lubman RL, and Crandall ED. Alveolar epithelial type I cells express sodium transport proteins. AmJRespir Crit Care Med 159: A467, 1999.

    Google Scholar 

  15. Borok Z, Hami A, Danto SI, Lubman RL, Kim KJ, and Crandall ED. Effects of EGF on alveolar epithelial junctional permeability and active sodium transport. Am J Physiol 270: L559–L565, 1996.

    PubMed  CAS  Google Scholar 

  16. Borok Z, Mihyu S, Fernandes VF, Zhang XL, Kim KJ, and Lubman RL. KGF prevents hyperoxia-induced reduction of active ion transport in alveolar epithelial cells. Am J Physiol 276: C1352–C1360, 1999.

    PubMed  CAS  Google Scholar 

  17. Campbell AR, Folkesson HG, Berthiaume Y, Gutkowska J, Suzuki S, and Matthay MA. Alveolar epithelial fluid clearance persists in the presence of moderate left atrial hypertension in sheep. J Appl Physiol 86: 139–151, 1999.

    PubMed  CAS  Google Scholar 

  18. Carstairs JR, Nimmo A J, and Barnes PJ. Autoradiographic visualization of beta- adrenoceptor subtypes in human lung. Am Rev Respir Dis 132: 541–547, 1985.

    PubMed  CAS  Google Scholar 

  19. Carter EP, Matthay MA, Farinas J, and Verkman AS. Transalveolar osmotic and diffusional water permeability in intact mouse lung measured by a novel surface fluorescence method. J Gen Physiol 108: 133–142, 1996.

    Article  PubMed  CAS  Google Scholar 

  20. Charron PD, Fawley JP, and Maron MB. Effect of epinephrine on alveolar liquid clearance in the rat. J Appl Physiol 87: 611–618, 1999.

    PubMed  CAS  Google Scholar 

  21. Clerici C and Matthay MA. Hypoxia regulates gene expression of alveolar epithelial transport proteins. J Appl Physiol 88: 1890–1896, 2000.

    PubMed  CAS  Google Scholar 

  22. Conner ER, Ware LB, Modin G, and Matthay MA. Elevated pulmonary edema fluid concentrations of soluble intercellular adhesion molecule-1 in patients with acute lung injury: biological and clinical significance. Chest 116: 83S-84S, 1999.

    Article  PubMed  CAS  Google Scholar 

  23. Crandall ED, Heming TA, Palombo RL, and Goodman BE. Effects of terbutaline on sodium transport in isolated perfused rat lung. J Appl Physiol 60: 289–294, 1986.

    PubMed  CAS  Google Scholar 

  24. Dobbs L, Gonzales R, Matthay MA, Carter EP, Allen L, and Verkman AS. Highly water-permeable type I alveolar epithelial cells confer high transalveolar water permeability between the airspace and vasculature in rat lung. Proc Natl Acad Sci USA 95: 2991–2996, 1998.

    Article  PubMed  CAS  Google Scholar 

  25. Dobbs LG, Gonzalez R, Matthay MA, Carter EP, Allen L, and Verkman AS. Highly water-permeable type I alveolar epithelial cells confer high water permeability between the airspace and vasculature in rat lung. Proc Natl Acad Sci USA 95: 2991–2996, 1998.

    Article  PubMed  CAS  Google Scholar 

  26. Egli M, Cook S, Hugh O, Hummler E, Nicod P, and Scherrer U. Delayed resolution of thiourea-induced pulmonary edema in mice with defective sodium transport-dependent alveolar fluid clearance. FASEB J, 2001. In press

    Google Scholar 

  27. Egli M, Cook S, Hugh O, Nicod P, and Scherrer U. Intravenous keratinocyte growth factor stimulates alveolar fluid clearance and accelerates the resolution of thiourea-induced pulmonary edema in mice. FASEB 7, 2001. In press.

    Google Scholar 

  28. Egli M, Sartori C, Duplain H, Lepori M, Hummler E, Nicod P, Rossier B, and Scherrer U. Impaired alveolar fluid clearance and augmented susceptibility to lung edema in mice with defective amiloride sensitive sodium transport. FASEB J 14: A127, 2000.

    Google Scholar 

  29. Fabisiak JP, Vesell ES, and Ranneis DE. Interactions of beta adrenergic antagonists with isolated rat alveolar type II pneumocytes. I. Analysis, characterization and regulation of specific beta adrenergic receptors. J Pharmacol Exp Ther 241: 722–727, 1987.

    PubMed  CAS  Google Scholar 

  30. Factor P, Dumasius V, Azzam ZS, and Sznajder JI. Overexpression of the beta2-adrenergic receptor increases lung liquid clearance by increasing sensitivity to endogenous catecholamines in rats. Am J Respir Crit Care Med 161: A447, 2000.

    Google Scholar 

  31. Factor P, Dumasius V, Saldias F, and Sznajder JI. Adenoviral-mediated overexpression of the NA,K-ATPase betal subunit gene increases lung edema clearance and improves survival during acute hyperoxic lung injury in rats. Chest 116: 24S-25S, 1999.

    Article  PubMed  CAS  Google Scholar 

  32. Factor P, Saldias F, Ridge K, Dumasius V, Zabner J, Jaffe HA, Blanco G, Barnard M, Mercer R, Perrin R, and Sznajder JI. Augmentation of lung liquid clearance via adenovirus-mediated transfer of a Na,K-ATPase betal subunit gene. J Clin Invest 102: 1421–1430, 1998.

    Article  PubMed  CAS  Google Scholar 

  33. Folkesson HG, Matthay MA, Hasegawa H, Kheradmand F, and Verkman AS. Transcellular water transport in lung alveolar epithelium through mercury-sensitive water channels. Proc Natl Acad Sci USA 91: 4970–4974, 1994.

    Article  PubMed  CAS  Google Scholar 

  34. Folkesson HG, Nitenberg G, Oliver BL, Jayr C, Albertine KH, and Matthay MA. Upregulation of alveolar epithelial fluid transport after subacute lung injury in rats from bleomycin. Am J Physiol 275: L478-L490, 1998.

    PubMed  CAS  Google Scholar 

  35. Folkesson HG, Noriin A, and Baines DL. Salt and water transport across the alveolar epithelium in the developing lung: Correlations between function and recent molecular biology advances (Review). IntJ MolMed 2: 515–531, 1998.

    CAS  Google Scholar 

  36. Folkesson HG, Noriin A, Wang Y, Abedinpour P, and Matthay MA. Dexamethasone and thyroid hormone pretreatment upregulate alveolar epithelial fluid clearance in adult rats. J Appl Physiol 88: 416–424, 2000.

    Article  PubMed  CAS  Google Scholar 

  37. Folkesson HG, Pittet JF, Nitenberg G, and Matthay MA. Transforming growth factor-alpha increases alveolar liquid clearance in anesthetized ventilated rats. Am J Physiol 271:L236-L244, 1996.

    PubMed  CAS  Google Scholar 

  38. Frank JA, Wang Y, and Matthay MA. Ventilator-associated lung injury: does low tidal volume ventilation protect the alveolar epithelial barrier in a rat model of acid-induced lung injury’. Am J Respir Crit Care Med 161: A725, 2000.

    Google Scholar 

  39. Frank JA, Wang Y, Osorio O, and Matthay MA. Beta-adrenergic agonist therapy accelerates the resolution of hydrostatic pulmonary edema in sheep and rats. J Appl Physiol 89: 1255–1265, 2000.

    PubMed  CAS  Google Scholar 

  40. Fukuda N, Barbry P, and Matthay MA. CFTR controls cAMP-regulated isoosmolar alveolar fluid transport in the distal airspaces of the mouse lung. Am J Respir Crit Care Med 161: A448, 2000.

    Google Scholar 

  41. Fukuda N, Folkesson HG, and Matthay MA. Relationship of interstitial fluid volume to alveolar fluid clearance in mice: ventilated vs. in situ studies. J Appl Physiol 89: 672–679, 2000.

    PubMed  CAS  Google Scholar 

  42. Fukuda N, Mcgraw DW, Liggert SB, Folkesson HG, and Matthay MA. Overexpression of the beta-2 adrenergic receptor in alveolar type II cells upregulates alveolar epithelial fluid transport in mice. FASEB J 14: A129, 2000.

    Google Scholar 

  43. Garat C, Carter EP, and Matthay MA. New in situ mouse model to quantify alveolar epithelial fluid clearance. J Appl Physiol 84: 1763–1767, 1998.

    PubMed  CAS  Google Scholar 

  44. Garat C, Meignan M, Matthay MA, Luo DF, and Jayr C. Alveolar epithelial fluid clearance mechanisms are intact after moderate hyperoxic lung injury in rats. Chest 111: 1381–1388, 1997.

    Article  PubMed  CAS  Google Scholar 

  45. Garat C, Rezaiguia S, Meignan M, D’Ortho MP, Harf A, Matthay MA, and Jayr C. Alveolar endotoxin increases alveolar liquid clearance in rats. J Appl Physiol 79: 2021–2028, 1995.

    PubMed  CAS  Google Scholar 

  46. Goodman BE, Anderson JL, and Clemens JW. Evidence for regulation of sodium transport from airspace to vascular space by cAMP. Am J Physiol 257: L86–L93, 1989.

    PubMed  CAS  Google Scholar 

  47. Goodman BE, Kim KJ, and Crandall ED. Evidence for active sodium transport across alveolar epithelium of isolated rat lung. J Appl Physiol 62: 2460–2466, 1987.

    PubMed  CAS  Google Scholar 

  48. Gowen CW, Jr., Lawson EE, Gingras J, Boucher RC, Gatzy JT, and Knowles MR. Electrical potential difference and ion transport across nasal epithelium of term neonates: correlation with mode of delivery, transient tachypnea of the newborn, and respiratory rate. J Pediatr 113: 121–127, 1988.

    Article  PubMed  Google Scholar 

  49. Guery BP, Mason CM, Dobard EP, Beaucaire G, Summer WR, and Nelson S. Keratinocyte growth factor increases transalveolar sodium reabsorption in normal and injured rat lungs. Am J Respir Crit Care Med 155: 1777–1784, 1997.

    PubMed  CAS  Google Scholar 

  50. Guo J, Yi ES, Havill AM, Sarosi I, Whitcomb L, Yin S, Middleton SC, Piguet P, and Ulich TR. Intravenous keratinocyte growth factor protects against experimental pulmonary injury. Am J Physiol 275: L800–L805, 1998.

    PubMed  CAS  Google Scholar 

  51. Guo Y, Duvall MD, Crow JP, and Matalon S. Nitric oxide inhibits Na+ absorption across ultured alveolar type II monolayers. Am J Physiol 274: L369–L377, 1998.

    PubMed  CAS  Google Scholar 

  52. Heberlein W, Wodopia R, Bartsch P, and Mairbaurl H. Possible role of ROS as mediators of hypoxia-induced ion transport inhibition of alveolar epithelial cells. Am J Physiol Lung Cell Mol Physiol 278: L640–L648, 2000.

    PubMed  CAS  Google Scholar 

  53. Hummler E, Barker P, Gatzy J, Beermann F, Verdumo C, Schmidt A, Boucher R, and Rossier BC. Early death due to defective neonatal lung liquid clearance in alpha- ENaC-deficient mice. Nat Genet 12: 325–328, 1996.

    Article  PubMed  CAS  Google Scholar 

  54. Hummler E, Barker P, Talbot C, Wang Q, Verdumo C, Grubb B, Gatzy J, Burnier M, Horisberger JD, Beermann F, Boucher R, and Rossier BC. A mouse model for the renal salt-wasting syndrome pseudohypoaldosteronism. Proc Natl Acad Sci USA 94: 11710–11715, 1997.

    Article  PubMed  CAS  Google Scholar 

  55. Inglis SK, Corboz MR, Taylor AE, and Ballard ST. Regulation of ion transport across porcine distal bronchi. Am J Physiol 270: L289–L297, 1996.

    PubMed  CAS  Google Scholar 

  56. Jayr C, Garat C, Meignan M, Pittet JF, Zelter M, and Matthay MA. Alveolar liquid and protein clearance in anesthetized ventilated rats. J Appl Physiol 76: 2636–2642, 1994.

    Article  PubMed  CAS  Google Scholar 

  57. Jiang X, Ingbar DH, and O’Grady SM. Adrenergic stimulation of Na+ transport across alveolar epithelial cells involves activation of apical CI- channels. Am J Physiol 275: C1610-C1620, 1998.

    PubMed  CAS  Google Scholar 

  58. Junor RW, Benjamin AR, Alexandrou D, Guggino SE, and Walters DV. A novel role for cyclic nucleotide-gated cation channels in lung liquid homeostasis in sheep. J Physiol (Lond) 520 Pt 1: 255–260, 1999.

    Article  CAS  Google Scholar 

  59. Knowles MR, Carson JL, Collier AM, Gatzy JT, and Boucher RC. Measurements of nasal transepithelial electric potential differences in normal human subjects in vivo. Am Rev Respir Dis 124: 484–490, 1981.

    PubMed  CAS  Google Scholar 

  60. Lane SM, Maender KC, Awender NE, and Maron MB. Adrenal epinephrine increases alveolar liquid clearance in a canine model of neurogenic pulmonary edema. Am J Respir Crit Care Med 158: 760–768, 1998.

    PubMed  CAS  Google Scholar 

  61. Lasnier JM, Wangensteen OD, Schmitz LS, Gross CR, and Ingbar DH. Terbutaline stimulates alveolar fluid resorption in hyperoxic lung injury. J Appl Physiol 81: 1723–1729, 1996.

    PubMed  CAS  Google Scholar 

  62. Lazrak A, Samanta A, and Matalon S. Biophysical properties and molecular characterization of amiloride- sensitive sodium channels in A549 cells. Am J Physiol Lung Cell Mol Physiol 278: L848–L857, 2000.

    PubMed  CAS  Google Scholar 

  63. Lecuona E, Saldias F, Cornelias A, Ridge K, Guerrero C, and Sznajder JI. Ventilator-associated lung injury decreases lung ability to clear edema in rats. Am J Respir Crit Care Med 159: 603–609, 1999.

    PubMed  CAS  Google Scholar 

  64. Ma T, Fukuda N, Song Y, Matthay MA, and Verkman AS. Lung fluid transport in aquaporin-5 knockout mice. J Clin Invest 105: 93–100, 2000.

    Article  PubMed  CAS  Google Scholar 

  65. Mairbaurl H, Wodopia R, Eckes S, Schulz S, and Bartsch P. Impairment of cation transport in A549 cells and rat alveolar epithelial cells by hypoxia. Am J Physiol 273: L797–L806, 1997.

    PubMed  CAS  Google Scholar 

  66. Mason RJ, Williams MC, Widdicombe JH, Sanders MJ, Misfeldt DS, and Berry LC, Jr. Transepithelial transport by pulmonary alveolar type II cells in primary culture. Proc Natl Acad Sci USA 79: 6033–6037, 1982.

    Article  PubMed  CAS  Google Scholar 

  67. Matalon S, Benos DJ, and Jackson RM. Biophysical and molecular properties of amiloride-inhibitable Na+ channels in alveolar epithelial cells. Am J Physiol 271: L1–22, 1996.

    PubMed  CAS  Google Scholar 

  68. Matalon S and O’Brodovich H. Sodium channels in alveolar epithelial cells: molecular characterization, biophysical properties, and physiological significance. Annu Rev Physiol 61: 627–661, 1999.

    Article  PubMed  CAS  Google Scholar 

  69. Matthay MA, Flori HR, Conner ER, and Ware LB. Alveolar epithelial fluid transport: basic mechanisms and clinical relevance. Proc Assoc Am Physicians 110: 496–505, 1998.

    PubMed  CAS  Google Scholar 

  70. Matthay MA, Folkesson HG, and Verkman AS. Salt and water transport across alveolar and distal airway epithelia in the adult lung. Am J Physiol 270: L487–L503, 1996.

    PubMed  CAS  Google Scholar 

  71. Matthay MA, Geiser T, Matalon S, and Ischiropoulos H. Oxidant-mediated lung injury in the acute respiratory distress syndrome. Crit Care Med 27: 2028–2030, 1999.

    Article  PubMed  CAS  Google Scholar 

  72. Matthay MA and Wiener-Kronish JP. Intact epithelial barrier function is critical for the resolution of alveolar edema in humans. Am Rev Respir Dis 142: 1250–1257, 1990.

    PubMed  CAS  Google Scholar 

  73. Middleton JP. Direct regulation of the Na,K pump by signal transduction mechanisms. Miner Electrolyte Metab 22: 293–302, 1996.

    PubMed  CAS  Google Scholar 

  74. Minakata Y, Suzuki S, Grygorczyk C, Dagenais A, and Berthiaume Y. Impact of beta- adrenergic agonist on Na+ channel and Na+-K+-ATPase expression in alveolar type II cells. Am J Physiol 275: L414–L422, 1998.

    PubMed  CAS  Google Scholar 

  75. Modelska K, Matthay MA, Brown LA, Deutch E, Lu LN, and Pittet JF. Inhibition of beta- adrenergic-dependent alveolar epithelial clearance by oxidant mechanisms after hemorrhagic shock. Am J Physiol 276: L844–L857, 1999.

    PubMed  CAS  Google Scholar 

  76. Newman V, Gonzalez RF, Matthay MA, and Dobbs LG. A novel alveolar type I cell-specific biochemical marker of human acute lung injury. Am J Respir Crit Care Med 161:990–995, 2000.

    PubMed  CAS  Google Scholar 

  77. Noriin A, Finley N, Abedinpour P, and Folkesson HG. Alveolar liquid clearance in the anesthetized ventilated guinea pig. Am J Physiol 274: L235–L243, 1998.

    Google Scholar 

  78. O’Brodovich H, Canessa C, Ueda J, Rafii B, Rossier BC, and Edelson J. Expression of the epithelial Na+ channel in the developing rat lung. Am J Physiol 265: C491–C496, 1993.

    PubMed  Google Scholar 

  79. O’Brodovich H, Hannam V, Seear M, and Mullen JBM. Amiloride impairs lung water clearance in newborn guinea pigs. J Appl Physiol 68: 1758–1762, 1990.

    PubMed  Google Scholar 

  80. Olivera WG, Ridge KM, and Sznajder JI. Lung liquid clearance and Na,K-ATPase during acute hyperoxia and recovery in rats. Am J Respir Crit Care Med 152: 1229–1234, 1995.

    PubMed  CAS  Google Scholar 

  81. Ouiddir A, Planes C, Fernandes I, VanHesse A, and Clerici C. Hypoxia upregulates activity and expression of the glucose transporter GLUTI in alveolar epithelial cells. Am J Respir Cell Mol Biol 21: 710–718, 1999.

    PubMed  CAS  Google Scholar 

  82. Panos RJ, Bak PM, Simonet WS, Rubin JS, and Smith LJ. Intratracheal instillation of keratinocyte growth factor decreases hyperoxia-induced mortality in rats. J Clin Invest 96: 2026–2033, 1995.

    Article  PubMed  CAS  Google Scholar 

  83. Pittet JF, Brenner TJ, Modelska K, and Matthay MA. Alveolar liquid clearance is increased by endogenous catecholamines in hemorrhagic shock in rats. J Appl Physiol 81:830–837, 1996.

    PubMed  CAS  Google Scholar 

  84. Pittet JF, Lu M, Modelska K, and Matthay MA. Role of nitric oxide in downregulating alveolar fluid clearance by a NFKB mechanisms in rats after hemorragic shock. J Immunol In review, 2000.

    Google Scholar 

  85. Pittet JF, Mackersie RC, Martin TR, and Matthay MA. Biological markers of acute lung injury: prognostic and pathogenetic significance. Am J Respir Crit Care Med 155: 1187–1205, 1997.

    PubMed  CAS  Google Scholar 

  86. Pittet JF, Wiener-Kronish JP, McElroy MC, Folkesson HG, and Matthay MA. Stimulation of lung epithelial liquid clearance by endogenous release of catecholamines in septic shock in anesthetized rats. J Clin Invest 94: 663–671, 1994.

    Article  PubMed  CAS  Google Scholar 

  87. Pittet JF, Wiener-Kronish JP, Serikov V, and Matthay MA. Resistance of the alveolar epithelium to injury from septic shock in sheep. Am J Respir Crit Care Med 151: 1093–1100, 1995.

    PubMed  CAS  Google Scholar 

  88. Planes C, Escoubet B, Blot-Chabaud M, Friedlander G, Farman N, and Clerici C. Hypoxia downregulates expression and activity of epithelial sodium channels in rat alveolar epithelial cells. Am J Respir Cell Mol Biol 17: 508–518, 1997.

    PubMed  CAS  Google Scholar 

  89. Planes C, Friedlander G, Loiseau A, Amiel C, and Clerici C. Inhibition of Na-K-ATPase activity after prolonged hypoxia in an alveolar epithelial cell line. Am J Physiol 271: L70–L78, 1996.

    PubMed  CAS  Google Scholar 

  90. Rafii B, Tanswell AK, Otulakowski G, Pitkanen O, Belcastro-Taylor R, and O’Brodovich H. O2-induced ENaC expression is associated with NF-kappaB activation and blocked by superoxide scavenger. Am J Physiol 275: L764–L770, 1998.

    PubMed  CAS  Google Scholar 

  91. Reddy MM, Light MJ, and Quinton PM. Activation of the epithelial Na+ channel (ENaC) requires CFTR CI- channel function. Nature 402: 301–304, 1999.

    Article  PubMed  CAS  Google Scholar 

  92. Rezaiguia S, Garat C, Delclaux C, Meignan M, Fleury J, Legrand P, Matthay MA, and Jayr C. Acute bacterial pneumonia in rats increases alveolar epithelial fluid clearance by a tumor necrosis factor-alpha-dependent mechanism. J Clin Invest 99: 325–335, 1997.

    Article  PubMed  CAS  Google Scholar 

  93. Rokaw MD, Sarac E, Lechman E, West M, Angeski J, Johnson JP, and Zeidel ML. Chronic regulation of transepithelial Na+ transport by the rate of apical Na+ entry. Am J Physiol 270: C600–C607, 1996.

    PubMed  CAS  Google Scholar 

  94. Sakuma T, Folkesson HG, Suzuki S, Okaniwa G, Fujimura S, and Matthay MA. Beta- adrenergic agonist stimulated alveolar fluid clearance in ex vivo human and rat lungs. Am J Respir Crit Care Med 155: 506–512, 1997.

    PubMed  CAS  Google Scholar 

  95. Sakuma T, Okaniwa G, Nakada T, Nishimura T, Fujimura S, and Matthay MA. Alveolar fluid clearance in the resected human lung. Am J Respir Crit Care Med 150: 305–310, 1994.

    PubMed  CAS  Google Scholar 

  96. Sakuma T, Tsukano C, Ishigaki M, Nambu Y, Osanai K, Toga H, Takahashi K, Ohya N, Kurihara T, Nishio M, and Matthay MA. Lung deflation impairs alveolar epithelial fluid transport in ischemic rabbit and rat lungs. Transplantation 69: 1785–1793, 2000.

    Article  PubMed  CAS  Google Scholar 

  97. Sakuma T, Tuchihara C, Ishigaki M, Osanai K, Nambu Y, Toga H, Takahashi K, Ohya N, Kurihara T, and Matthay MA. Denopamine, a beta (l)-adrenergic agonist, increases alveolar fluid clearance in ex vivo rat and guinea pig lungs. J Appl Physiol 90: 10–16, 2001.

    PubMed  CAS  Google Scholar 

  98. Saldias F, Lecuona E, Friedman E, Barnard ML, Ridge KM, and Sznajder JI. Modulation of lung liquid clearance by isoproterenol in rat lungs. Am J Physiol 274: L694–L701, 1998.

    PubMed  CAS  Google Scholar 

  99. Saldias FJ, Cornelias A, Ridge KM, Lecuona E, and Sznajder JI. Isoproterenol improves ability of lung to clear edema in rats exposed to hyperoxia. J Appl Physiol 87: 30–35, 1999.

    PubMed  CAS  Google Scholar 

  100. Saldias FJ, Lecuona E, Cornelias AP, Ridge KM, Rutschman DH, and Sznajder JI. Beta- adrenergic stimulation restores rat lung ability to clear edema in ventilator-associated lung injury. Am J Respir Crit Care Med 162: 282–287, 2000.

    PubMed  CAS  Google Scholar 

  101. Saldias FJ, Lecuona E, Cornelias AP, Ridge KM, and Sznajder JI. Dopamine restores lung ability to clear edema in rats exposed to hyperoxia. Am J Respir Crit Care Med 159: 626–633, 1999.

    PubMed  CAS  Google Scholar 

  102. Sartori C, Lepori M, Busch T, Duplain H, Hildebrandt W, Bartsch P, Nicod P, Falke KJ, and Scherrer U. Exhaled nitric oxide does not provide a marker of vascular endothelial function in healthy humans. Am J Respir Crit Care Med 160: 879–882, 1999.

    PubMed  CAS  Google Scholar 

  103. Sartori C, Lepori M, Duplain H, Maggiorini M., and Scherrer U. High-altitude exposure impairs the alveolar transepithelial sodium transport in humans. Am J Resp Crit Care Med 159: A355, 1999.

    Google Scholar 

  104. Sartori C, Lepori M, Maggiorini M, Allemann Y, Nicod P, and Scherrer U. Impairment of amiloride-sensitive sodium transport in individuals susceptible to high altitude pulmonary edema. FASEB J 12: A231, 1998.

    Google Scholar 

  105. Sartori C, Lipp E, Duplain H, Egli M, Hutter D, Allemann Y, Nicod P, and Scherrer U. Prevention of high-altitude pulmonary edema by beta-adrenergic stimulation of the alveolar transepithelial sodium transport. Am J Respir Crit Care Med 161: A415, 2000.

    Google Scholar 

  106. Scherrer U, Sartori C, Lepori M, Allemann Y, Duplain H, Trueb L, and Nicod P. High-altitude pulmonary edema: from exaggerated pulmonary hypertension to a defect in transepithelial sodium transport. Adv Exp Med Biol 474: 93–107, 1999.

    Article  PubMed  CAS  Google Scholar 

  107. Schneeberger EE and McCarthy KM. Cytochemical localization of Na+-K+-ATPase in rat type II pneumocytes. J Appl Physiol 60: 1584–1589, 1986.

    Article  PubMed  CAS  Google Scholar 

  108. Snyder PM. Liddle’s syndrome mutations disrupt cAMP-mediated translocation of the epithelial Na (+) channel to the cell surface. J Clin Invest 105: 45–53, 2000.

    Article  PubMed  CAS  Google Scholar 

  109. Song Y, Fukuda N, Bai C, Ma T, Matthay MA, and Verkman AS. Role of aquaporins in alveolar fluid clearance in neonatal and adult lung, and in oedema formation following acute lung injury: studies in transgenic aquaporin null mice. J Physiol 525 Pt 3: 771–779, 2000.

    Article  PubMed  CAS  Google Scholar 

  110. Song Y, Ma T, Matthay MA, and Verkman AS. Role of aquaporin-4 in airspace-to-capillary water permeability in intact mouse lung measured by a novel gravimetric method. J Gen Physiol 115: 17–27, 2000.

    Article  PubMed  CAS  Google Scholar 

  111. Staub NC. Pulmonary edema. Physiol Rev 54: 678–811, 1974.

    Article  PubMed  CAS  Google Scholar 

  112. Staub O, Gautschi I, Ishikawa T, Breitschopf K, Ciechanover A, Schild L, and Rotin D. Regulation of stability and function of the epithelial Na+ channel (ENaC) by ubiquitination. EMBOJ 16: 6325–6336, 1997.

    Article  CAS  Google Scholar 

  113. Stern M, Ulrich K, Robinson C, Copeland J, Griesenbach U, Masse C, Cheng S, Munkonge F, Geddes D, Berthiaume Y, and Alton E. Pretreatment with cationic lipid-mediated transfer of the Na+K+-ATPase pump in a mouse model in vivo augments resolution of high permeability pulmonary oedema. Gene Ther 7: 960–966, 2000.

    Article  PubMed  CAS  Google Scholar 

  114. Stutts MJ, Canessa CM, Olsen JC, Hamrick M, Cohn JA, Rossier BC, and Boucher RC. CFTR as a cAMP-dependent regulator of sodium channels. Science 269: 847–850, 1995.

    Article  PubMed  CAS  Google Scholar 

  115. Suzuki S, Noda M, Sugita M, Ono S, Koike K, and Fujimura S. Impairment of transalveolar fluid transport and lung Na (+)-K (+)-ATPase function by hypoxia in rats. J Appl Physiol 87: 962–968, 1999.

    PubMed  CAS  Google Scholar 

  116. Suzuki S, Sugita M, Noda M, Tsubochi H, and Fujimura S. Effects of intraalveolar oxygen concentration on alveolar fluid absorption and metabolism in isolated rat lungs. Respir Physiol 115: 325–332, 1999.

    Article  PubMed  CAS  Google Scholar 

  117. Sweezey N, Tchepichev S, Gagnon S, Fertuck K, and O’Brodovich H. Female gender hormones regulate mRNA levels and function of the rat lung epithelial Na channel. Am J Physiol 274: C379–C386, 1998.

    PubMed  CAS  Google Scholar 

  118. Sznajder JI, Olivera WG, Ridge KM, and Rutschman DH. Mechanisms of lung liquid clearance during hyperoxia in isolated rat lungs. Am J Respir Crit Care Med 151: 1519–1525, 1995.

    PubMed  CAS  Google Scholar 

  119. Sznajder JI, Ridge KM, Yeates DB, Ilekis J, and Olivera W. Epidermal growth factor increases lung liquid clearance in rat lungs. J Appl Physiol 85: 1004–1010, 1998.

    PubMed  CAS  Google Scholar 

  120. Tchepichev S, Ueda J, Canessa C, Rossier BC, and O’Brodovich H. Lung epithelial Na channel subunits are differentially regulated during development and by steroids. Am J Physiol 269: C805–C812, 1995.

    PubMed  CAS  Google Scholar 

  121. Tibayan FA, Chesnutt AN, Folkesson HG, Eandi J, and Matthay MA. Dobutamine increases alveolar liquid clearance in ventilated rats by beta-2 receptor stimulation. Am J Respir Crit Care Med 156: 438–444, 1997.

    PubMed  CAS  Google Scholar 

  122. Tohda H and Marunaka Y. Insulin-activated amiloride-blockable nonselective cation and Na+ channels in the fetal distal lung epithelium. Gen Pharmacol 26: 755–763, 1995.

    Article  PubMed  CAS  Google Scholar 

  123. Tomlinson LA, Carpenter TC, Baker EH, Bridges JB, and Weil JV. Hypoxia reduces airway epithelial sodium transport in rats. Am J Physiol 277: L881–L886, 1999.

    PubMed  CAS  Google Scholar 

  124. Verghese GM, McCormick-Shannon K, Mason RJ, and Matthay MA. Hepatocyte growth factor and keratinocyte growth factor in the pulmonary edema fluid of patients with acute lung injury. Biologic and clinical significance. Am J Respir Crit Care Med 158: 386–394, 1998.

    PubMed  CAS  Google Scholar 

  125. Verghese GM, Ware LB, Matthay BA, and Matthay MA. Alveolar epithelial fluid transport and the resolution of clinically severe hydrostatic pulmonary edema. J Appl Physiol 87: 1301–1312, 1999.

    PubMed  CAS  Google Scholar 

  126. Verkman AS. Role of aquaporin water channels in kidney and lung. Am J Med Sci 316: 310–320, 1998.

    Article  PubMed  CAS  Google Scholar 

  127. Verkman AS, Yang B, Song Y, Manley GT, and Ma T. Role of water channels in fluid transport studied by phenotype analysis of aquaporin knockout mice. Exp Physiol 85 Spec No: 233S–241S, 2000.

    Article  PubMed  CAS  Google Scholar 

  128. Wang Y, Folkesson HG, Jayr C, Ware LB, and Matthay MA. Alveolar epithelial fluid transport can be simultaneously upregulated by both KGF and beta-agonist therapy. J Appl Physiol 87: 1852–1860, 1999.

    PubMed  CAS  Google Scholar 

  129. Wang Y, Jayr C, Folkesson HG, and Matthay MA. Alveolar epithelial fluid transport can be upregulated simultaneously in rats by two different mechanisms. Chest 116: 98S–100S, 1999.

    Article  PubMed  CAS  Google Scholar 

  130. Ware LB, Geiser T, Nuckton TJ, Daniel B, and Matthay MA. Elevated levels of markers of apoptosis in the biological fluids of patients with early acute lung injury. Am J Respir Crit Care Med 161: A380, 2000.

    Google Scholar 

  131. Ware LB and Matthay MA. The acute respiratory distress syndrome. N Engl J Med 342: 1334–1349, 2000.

    Article  PubMed  CAS  Google Scholar 

  132. Ware LB and Matthay MA. Alveolar fluid clearance is impaired in the majority of patients with acute lung injury and the acute respiratory distress syndrome. Am J Resp Crit Care Med, 2001. In press.

    Google Scholar 

  133. Waters CM, Ridge KM, Sunio G, Venetsanou K, and Sznajder JI. Mechanical stretching of alveolar epithelial cells increases Na (+)-K (+)- ATPase activity. J Appl Physiol 87: 715–721, 1999.

    PubMed  CAS  Google Scholar 

  134. Wiener-Kronish JP, Albertine KH, and Matthay MA. Differential responses of the endothelial and epithelial barriers of the lung in sheep to Escherichia coli endotoxin. J Clin Invest 88: 864–875, 1991.

    Article  PubMed  CAS  Google Scholar 

  135. Wodopia R, Ko HS, Billian J, Wiesner R, Bartsch P, and Mairbaurl H. Hypoxia decreases proteins involved in epithelial electrolyte transport in A549 cells and rat lung. Am J Physiol Lung Cell Mol Physiol 279: L1110–L1119, 2000.

    PubMed  CAS  Google Scholar 

  136. Yano T, Deterding RR, Simonet WS, Shannon JM, and Mason RJ. Keratinocyte growth factor reduces lung damage due to acid instillation in rats. Am J Respir Cell Mol Biol 15:433–442, 1996.

    PubMed  CAS  Google Scholar 

  137. Yi ES, Williams ST, Lee H, Malicki DM, Chin EM, Yin S, Tarpley J, and Ulich TR. Keratinocyte growth factor ameliorates radiation- and bleomycine induced lung injury and mortality. Am J Pathol 149: 1963–1970, 1996.

    PubMed  CAS  Google Scholar 

  138. Yue G and Matalon S. Mechanisms and sequelae of increased alveolar fluid clearance in hyperoxic rats. Am J Physiol 272: L407–L412, 1997.

    PubMed  CAS  Google Scholar 

  139. Yue G, Russell WJ, Benos DJ, Jackson RM, Olman MA, and Matalon S. Increased expression and activity of sodium channels in alveolar type II cells of hyperoxic rats. Proc Natl Acad Sci USA 92: 8418–8422, 1995.

    Article  PubMed  CAS  Google Scholar 

  140. Zuege D, Suzuki S, and Berthiaume Y. Increase of lung sodium-potassium-ATPase activity during recovery from high-permeability pulmonary edema. Am J Physiol 271: L896–L909, 1996.

    PubMed  CAS  Google Scholar 

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Sartori, C., Matthay, M.A., Scherrer, U. (2001). Transepithelial sodium and water transport in the lung. In: Roach, R.C., Wagner, P.D., Hackett, P.H. (eds) Hypoxia. Advances in Experimental Medicine and Biology, vol 502. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-3401-0_21

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