Format

Send to

Choose Destination
See comment in PubMed Commons below
Am J Physiol Renal Physiol. 2005 Oct;289(4):F692-8. Epub 2005 May 31.

Collecting duct-specific knockout of the endothelin A receptor alters renal vasopressin responsiveness, but not sodium excretion or blood pressure.

Author information

1
Division of Nephrology, Univ. of Utah Health Sciences Center, 1900 East, 30 North, Salt Lake City, UT 84132, USA.

Abstract

Collecting duct (CD)-specific knockout (KO) of endothelin-1 (ET-1) causes hypertension, impaired ability to excrete a Na load, and enhanced CD sensitivity to the hydrosmotic effects of vasopressin (AVP). CD express the two known ET receptors, ET(A) and ET(B); in the current study, the role of the CD ET(A) receptor in mediating ET-1 actions on this nephron segment was evaluated. The ET(A) receptor gene was selectively disrupted in CD (CD ET(A) KO). CD ET(A) KO mice had no differences in systemic blood pressure, Na or K excretion, and plasma aldosterone or renin activity in response to a normal- or a high-Na diet compared with controls. During normal water intake, urinary osmolality (Uosm), plasma Na concentration, and plasma osmolality were not affected, but plasma AVP concentration was increased in CD ET(A) KO animals (0.57 +/- 0.25 pg/ml in controls and 1.30 +/- 0.29 pg/ml in CD ET(A) KO mice). CD ET(A) KO mice had a modestly enhanced ability to excrete an acute, but not a chronic, water load. DDAVP infusion increased Uosm similarly; however, CD ET(A) KO mice had a more rapid subsequent fall in Uosm during sustained DDAVP administration. CD suspensions from CD ET(A) KO mice had a 30-40% reduction in AVP- and forskolin-stimulated cAMP accumulation. These data indicate that CD ET(A) KO decreases renal sensitivity to the urinary concentrating effects of AVP and suggest that activation of the ET(A) receptor downregulates ET-1 inhibition of AVP actions in the CD. Furthermore, the CD ET(A) receptor does not appear to be involved in modulation of systemic blood pressure or renal Na excretion under physiological conditions.

PMID:
15928212
DOI:
10.1152/ajprenal.00100.2005
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center