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

Jun 2, 2005American journal of physiology. Renal physiology

Removing the endothelin A receptor in kidney collecting ducts changes water balance response but not salt removal or blood pressure

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

CD ET(A) knockout mice show a 30-40% reduction in cAMP accumulation in response to vasopressin.

Knockout of the endothelin-1 receptor in the collecting duct leads to hypertension and impaired sodium excretion.
Increased plasma vasopressin concentration was observed in CD ET(A) knockout mice compared to controls.
These knockout mice exhibited a modestly enhanced ability to excrete acute water loads.
During sustained vasopressin administration, CD ET(A) knockout mice experienced a more rapid decrease in urinary osmolality.
No differences in systemic blood pressure or renal sodium excretion were observed under normal dietary conditions.

AI simplified

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.

Full Text

Full text is available at the source.

View full text ↗

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

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief