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 journalArticle

87 Citations (Scopus)

Abstract

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)
JournalAmerican Journal of Physiology - Renal Physiology
Volume288
Issue number5 57-5
DOIs
StatePublished - May 2005

Fingerprint

Endothelin-1
Vasopressins
Osmolar Concentration
Urine
Aquaporin 2
Kidney
Water
Deamino Arginine Vasopressin
Messenger RNA
Colforsin
Drinking
Permeability
Suspensions
Phosphorylation

Keywords

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

ASJC Scopus subject areas

  • Physiology

Cite this

Collecting duct-specific knockout of endothelin-1 alters vasopressin regulation of urine osmolality. / Ge, Yuqiang; Ahn, Dowahn; Stricklett, Peter K.; Hughes, Alisa K.; Yanagisawa, Masashi; Verbalis, Joseph G.; Kohan, Donald E.

In: American Journal of Physiology - Renal Physiology, Vol. 288, No. 5 57-5, 05.2005.

Research output: Contribution to journalArticle

Ge, Yuqiang ; Ahn, Dowahn ; Stricklett, Peter K. ; Hughes, Alisa K. ; Yanagisawa, Masashi ; Verbalis, Joseph G. ; Kohan, Donald E. / Collecting duct-specific knockout of endothelin-1 alters vasopressin regulation of urine osmolality. In: American Journal of Physiology - Renal Physiology. 2005 ; Vol. 288, No. 5 57-5.
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