Abstract
Acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), remain leading factors for morbidity and mortality in critically ill patients. A significant aspect of ALI and ARDS is impaired alveolar fluid clearance (AFC). Improvements in therapies for these types of respiratory illnesses will require an understanding of the mechanisms that control AFC. The present study was designed to determine whether the administration of dobutamine decreases pulmonary edema and stimulates AFC in a rat model of lipopolysaccharide-induced lung injury. Adult male Sprague–Dawley rats were randomly divided into three groups: control, lipopolysaccharide, and lipopolysaccharide + dobutamine. The effect of dobutamine on AFC and the expression of aquaporin-1 and aquaporin-5 were examined. Lipopolysaccharide administration results in significant lung injury with impaired AFC, while dobutamine improves alveolar fluid reabsorption with elevation of aquaporin-1 and aquaporin-5. Our study indicates that dobutamine may enhance alveolar fluid reabsorption by increasing the expression of aquaporin-1 and aquaporin-5.
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References
Costa EL, Schettino IA, Schettino GP (2006) The lung in sepsis: guilty or innocent? Endocr Metab Immune Disord Drug Targets 6:213–216
Frutos-Vivar F, Ferguson ND, Esteban A (2006) Epidemiology of acute lung injury and acute respiratory distress syndrome. Semin Respir Crit Care Med 27:327–336
Ware LB, Michel A, Mattha Y (2001) Alveolar fluid clearance is impaired in the majority of patients with acute lung injury and the acute respiratory distress syndrome. Am J Respir Crit Care Med 163:1376–1383
Rojas M, Woods CR, Mora AL, Xu J, Brigham KL (2005) Endotoxin-induced lung injury in mice: structural, functional, and biochemical responses. Am J Physiol Lung Cell Mol Physiol 288:L333–L341
Sakuma T, Tuchihara C, Ishigaki M, Osanai K, Nambu Y, Toga H, Takahashi K, Ohya N, Kurihara T, Matthay MA (2001) Denopamine, a beta (1)-adrenergic agonist, increases alveolar fluid clearance in ex vivo rat and guinea pig lungs. J Appl Physiol 90(1):10–16
Sakuma T, Hida M, Nambu Y, Osanai K, Toga H, Takahashi K, Ohya N, Inoue M, Watanabe Y (2001) Effects of hypoxia on alveolar fluid transport capacity in rat lungs. J Appl Physiol 91:1766–1774
Sakuma T, Sagawa M, Hida M, Nambu Y, Osanai K, Toga H, Takahashi K, Ohya N, Matthay MA (2002) Time-dependent effect of pneumonectomy on alveolar epithelial fluid clearance in rat lungs. J Thorac Cardiovasc Surg 124:668–674
Ma T, Yang B, Gillespie A, Carlson EJ, Epstein CJ, Verkman AS (1998) Severely impaired urinary concentrating ability in transgenic mice lacking aquaporin-1 water channels. J Biol Chem 273:4296–4299
Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL, International Surviving Sepsis Campaign Guidelines Committee, American Association of Critical-Care Nurses, American College of Chest Physicians, American College of Emergency Physicians, Canadian Critical Care Society, European Society of Clinical Microbiology and Infectious Diseases, European Society of Intensive Care Medicine, European Respiratory Society, International Sepsis Forum, Japanese Association for Acute Medicine, Japanese Society of Intensive Care Medicine, Society of Critical Care Medicine, Society of Hospital Medicine, Surgical Infection Society, World Federation of Societies of Intensive and Critical Care Medicine (2008) Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock. Crit Care Med 36(1):296-327
Mutlu GM, Dumasius V, Burhop J, McShane PJ, Meng FJ, Welch L, Dumasius A, Mohebahmadi N, Thakuria G, Hardiman K, Matalon S, Hollenberg S, Factor P (2004) Upregulation of alveolar epithelial active Na+ transport is dependent on beta2-adrenergic receptor signaling. Circ Res 94:1091–1100
Saldias FJ, Lecuona E, Comellas AP, Ridge KM, Rutschman DH, Sznajder JI (2000) beta-adrenergic stimulation restores rat lung ability to clear edema in ventilator-associated lung injury. Am J Respir Crit Care Med 162:282–287
Sakuma T, Hida M, Nambu Y, Osanai K, Toga H, Takahashi K, Ohya N, Inoue M, Watanabe Y (2001) Beta1-adrenergic agonist is a potent stimulator of alveolar fluid clearance in hyperoxic rat lungs. Jpn J Pharmacol 85(2):161–166
Randrianarison N, Escoubet B, Ferreira C, Fontayne A, Fowler-Jaeger N, Clerici C, Hummler E, Rossier BC, Planès C (2007) beta-Liddle mutation of the epithelial sodium channel increases alveolar fluid clearance and reduces the severity of hydrostatic pulmonary edema in mice. J Physiol 582(Pt 2):777–788
Ware LB, Mathay MA (2000) The acute respiratory distress syndrome. N Engl J Med 342:1334–1349
Domeniconi RF, Orsi AM, Justulin LA, Leme Beu CC, Felisbino SL (2007) Aquaporin 9 (AQP9) localization in the adult dog testis excurrent ducts by immunohistochemistry. Anat Rec (Hoboken) 290:1519–1525
Woo J, Chae YK, Jang SJ, Kim MS, Baek JH, Park JC, Trink B, Ratovitski E, Lee T, Park B, Park M, Kang JH, Soria JC, Lee J, Califano J, Sidransky D, Moon C (2008) Membrane trafficking of AQP5 and cAMP dependent phosphorylation in bronchial epithelium. Biochem Biophys Res Commun 366:321–327
Kreda SM, Gynn MC, Fenstermacher DA, Boucher RC, Gabriel SE (2001) Expression and localization of epithelial aquaporins in the adult human lung. Am J Respir Cell Mol Biol 24:224–234
Agre P (2004) Aquaporin water channels (Nobel Lecture). Angew Chem Int Ed Engl 43:4278–4290
Dobbs LG, Gonzalez MA, Matthay EP, Carter LA, Verkman AS (1998) 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
Su X, Song Y, Jiang J, Bai C (2004) The role of aquaporin-1 (AQP1) expression in a murine model of lipopolysaccharide-induced acute lung injury. Respir Physiol Neurobiol 142:1–11
Tsubota K, Hirai S, King LS, Agre P, Ishida N (2001) Defective cellular trafficking of lacrimal gland aquaporin-5 in Sjögren’s syndrome. Lancet 357:688–689
Funaki H, Yamamoto T, Koyama Y, Kondo D, Yaoita E, Kawasaki K, Kobayashi H, Sawaguchi S, Abe H, Kihara I (1998) Localization and expression of AQP5 in cornea, serous salivary glands and pulmonary epithelial cells. Am J Physiol 275:C1151–C1157
Towne JE, Harrod KS, Krane CM, Menon AG (2000) Decreased expression of aquaporin (AQP)1 and AQP5 in mouse lung after acute viral infection. Am J Respir Cell Mol Biol 22:34–44
Hoffert JD, Chou CL, Fenton RA, Knepper MA (2005) Calmodulin is required for vasopressin-stimulated increase in cyclic AMP production in inner medullary collecting duct. J Biol Chem 280:13624–13630
Tamma G, Carmosino M, Svelto M, Valenti G (2005) Bradykinin signaling counteracts cAMP-elicited aquaporin 2 translocation in renal cells. J Am Soc Nephrol 16(10):2881–2889
Sidhaye V, Hoffert JD, King LS (2005) cAMP has distinct acute and chronic effects on aquaporin-5 in lung epithelial cells. J Biol Chem 280:3590–3596
Liggett SB, Bouvier M, Hausdorff WP, O’Dowd B, Caron MG, Lefkowitz RJ (1989) Altered patterns of agonist-stimulated cAMP accumulation in cells expressing mutant beta 2-adrenergic receptors lacking phosphorylation sites. Mol Pharmacol 36:641–646
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This study was supported by an ICU grant from the Sheng**g Hospital, China Medical University (No. 20072101).
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Wu, XM., Wang, HY., Li, GF. et al. Dobutamine Enhances Alveolar Fluid Clearance in a Rat Model of Acute Lung Injury. Lung 187, 225–231 (2009). https://doi.org/10.1007/s00408-009-9155-5
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DOI: https://doi.org/10.1007/s00408-009-9155-5