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

Yuqiang Ge, Dowahn Ahn, Peter K. Stricklett, Alisa K. Hughes, Masashi Yanagisawa, Joseph G. Verbalis, Donald E. Kohan

Research output: Contribution to journalReview articlepeer-review

95 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)F912-F920
JournalAmerican Journal of Physiology - Renal Physiology
Issue number5 57-5
StatePublished - May 2005


  • Adenosine 3′,5′-cyclic monophosphate
  • Aquaporin-2
  • Inner medullary collecting duct

ASJC Scopus subject areas

  • Physiology
  • Urology


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