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This Article Full Text Full Text (PDF) All Versions of this Article: 582/2/777    most recent jphysiol.2007.131078v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Randrianarison, N. Articles by Planès, C. Search for Related Content PubMed PubMed Citation Articles by Randrianarison, N. Articles by Planès, C. Related Collections Respiratory

¹ INSERM, U773, CRB3, Paris F-75018, France
² Université Denis Diderot-Paris7, Paris F-75018, France
³ INSERM, U772, Paris F-75005, France
⁴ CEFI IFR02, Université Denis Diderot-Paris7, Paris F-75018, France
⁵ Département de Pharmacologie et de Toxicologie, Université de Lausanne, 1005 Lausanne, Switzerland
⁶ Université de Versailles Saint-Quentin, Versailles F-78000, France

Transepithelial sodium transport via alveolar epithelial Na⁺ channels and Na⁺,K⁺-ATPase constitutes the driving force for removal of alveolar oedema fluid. Decreased activity of the amiloride-sensitive epithelial Na⁺ channel (ENaC) in the apical membrane of alveolar epithelial cells impairs sodium-driven alveolar fluid clearance (AFC) and predisposes to pulmonary oedema. We hypothesized that hyperactivity of ENaC in the distal lung could improve AFC and facilitate the resolution of pulmonary oedema. AFC and lung fluid balance were studied at baseline and under conditions of hydrostatic pulmonary oedema in the -Liddle (L) mouse strain harbouring a gain-of-function mutation (R⁵⁶⁶_stop) within the Scnn1b gene. As compared with wild-type (+/+), baseline AFC was increased by 2- and 3-fold in heterozygous (+/L) and homozygous mutated (L/L) mice, respectively, mainly due to increased amiloride-sensitive AFC. The ₂-agonist terbutaline stimulated AFC in +/+ and +/L mice, but not in L/L mice. Acute volume overload induced by saline infusion (40% of body weight over 2 h) significantly increased extravascular (i.e. interstitial and alveolar) lung water as assessed by the bloodless wet-to-dry lung weight ratio in +/+ and L/L mice, as compared with baseline. However, the increase was significantly larger in +/+ than in L/L groups (P = 0.01). Volume overload also increased the volume of the alveolar epithelial lining fluid in +/+ mice, indicating the presence of alveolar oedema, but not in L/L mice. Cardiac function as evaluated by echocardiography was comparable in both groups. These data show that constitutive ENaC activation improved sodium-driven AFC in the mouse lung, and attenuated the severity of hydrostatic pulmonary oedema.

(Received 26 February 2007; accepted after revision 12 April 2007; first published online 12 April 2007)
Corresponding author C. Planès: INSERM 773, CRB3, Faculté de Médecine Xavier Bichat, 16 rue Henri Huchard, BP 416, F-75870 Paris Cedex 18, France. Email: carole.planes{at}apr.aphp.fr

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