Collecting duct-specific knockout of endothelin-1 alters vasopressin regulation of urine osmolality

Am J Physiol Renal Physiol. 2005 May;288(5):F912-20. doi: 10.1152/ajprenal.00432.2004. Epub 2005 Jan 4.


In vitro studies suggest that endothelin-1 (ET-1) inhibits vasopressin (AVP)-stimulated water permeability in the collecting duct (CD). To evaluate the role of CD-derived ET-1 in regulating renal water metabolism, the ET-1 gene was selectively disrupted in the CD (CD ET-1 KO). During normal water intake, urinary osmolality (Uosm), plasma Na concentration, urine volume, and renal aquaporin-2 (AQP2) levels were unchanged, but plasma AVP concentration was reduced in CD ET-1 KO animals. CD ET-1 KO mice had impaired ability to excrete an acute, but not a chronic, water load, and this was associated with increased CD ET-1 mRNA in control, but not CD ET-1 KO, mice. In response to continuous infusion of 1-desamino-8-D-arginine vasopressin, CD ET-1 KO mice had greater increases in Uosm, V2 and AQP2 mRNA, and phosphorylation of AQP2. CD suspensions from CD ET-1 KO mice had enhanced AVP- and forskolin-stimulated cAMP accumulation. These data indicate that CD ET-1 KO increases renal sensitivity to the urinary concentrating effects of AVP and suggest that ET-1 functions as a physiological autocrine regulator of AVP action in the CD.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aquaporin 2
  • Aquaporins / genetics
  • Cyclic AMP / metabolism
  • Deamino Arginine Vasopressin / pharmacology
  • Drinking / physiology
  • Endothelin-1 / genetics*
  • Endothelin-1 / metabolism*
  • Integrases / genetics
  • Kidney Tubules, Collecting / physiology*
  • Mice
  • Mice, Knockout
  • Osmolar Concentration
  • Promoter Regions, Genetic
  • Receptors, Vasopressin / genetics
  • Renal Agents / pharmacology
  • Urine
  • Vasopressins / metabolism*
  • Water / metabolism
  • Water-Electrolyte Balance / drug effects
  • Water-Electrolyte Balance / physiology*


  • Aqp2 protein, mouse
  • Aquaporin 2
  • Aquaporins
  • Endothelin-1
  • Receptors, Vasopressin
  • Renal Agents
  • Water
  • Vasopressins
  • Cyclic AMP
  • Cre recombinase
  • Integrases
  • Deamino Arginine Vasopressin