ENaC activity in collecting ducts modulates NCC in cirrhotic mice

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• 作者：David Mordasini ; Dominique Loffing-Cueni…
• 关键词：Ascites ; Aldosterone ; Cirrhosis ; Cortical collecting ducts ; ENaC ; NCC
• 刊名：Pfl篓鹿gers Archiv - European Journal of Physiology
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：467
• 期：12
• 页码：2529-2539
• 全文大小：1,371 KB
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• 作者单位：David Mordasini (1) (2)
  Dominique Loffing-Cueni (5)
  Johannes Loffing (5)
  Rohrbach Beatrice (1) (2)
  Marc P. Maillard (3)
  Edith Hummler (4)
  Michel Burnier (3)
  Geneviève Escher (1) (2)
  Bruno Vogt (1) (2)
  
  1. Department of Nephrology, Hypertension and Clinical Pharmacology, Inselspital, Bern University Hospital, Bern, Switzerland
  2. Department of Clinical Research, University of Bern, Bern, Switzerland
  5. Institute of Anatomy, University of Zurich, Zurich, Switzerland
  3. Service of Nephrology and Hypertension, CHUV, Rue du Bugnon 17, CH-1005, Lausanne, Switzerland
  4. Department of Pharmacology and Toxicology, University of Lausanne, Rue du Bugnon 27, CH-1005, Lausanne, Switzerland
  
• 刊物主题：Human Physiology;
• 出版者：Springer Berlin Heidelberg
• ISSN：1432-2013

文摘

Cirrhosis is a frequent and severe disease, complicated by renal sodium retention leading to ascites and oedema. A better understanding of the complex mechanisms responsible for renal sodium handling could improve clinical management of sodium retention. Our aim was to determine the importance of the amiloride-sensitive epithelial sodium channel (ENaC) in collecting ducts in compensate and decompensate cirrhosis. Bile duct ligation was performed in control mice (CTL) and collecting duct-specific αENaC knockout (KO) mice, and ascites development, aldosterone plasma concentration, urinary sodium/potassium ratio and sodium transporter expression were compared. Disruption of ENaC in collecting ducts (CDs) did not alter ascites development, urinary sodium/potassium ratio, plasma aldosterone concentrations or Na,K-ATPase abundance in CCDs. Total αENaC abundance in whole kidney increased in cirrhotic mice of both genotypes and cleaved forms of α and γ ENaC increased only in ascitic mice of both genotypes. The sodium chloride cotransporter (NCC) abundance was lower in non-ascitic KO, compared to non-ascitic CTL, and increased when ascites appeared. In ascitic mice, the lack of αENaC in CDs induced an upregulation of total ENaC and NCC and correlated with the cleavage of ENaC subunits. This revealed compensatory mechanisms which could also take place when treating the patients with diuretics. These compensatory mechanisms should be considered for future development of therapeutic strategies. Keywords Ascites Aldosterone Cirrhosis Cortical collecting ducts ENaC NCC