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

Yuqiang Ge, Peter K. Stricklett, Alisa K. Hughes, Masashi Yanagisawa, Donald E. Kohan

Research output: Contribution to journalArticle

78 Citations (Scopus)

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, ETA and ETB; in the current study, the role of the CD ETA receptor in mediating ET-1 actions on this nephron segment was evaluated. The ETA receptor gene was selectively disrupted in CD (CD ETA KO). CD ETA 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 ETA KO animals (0.57 ± 0.25 pg/ml in controls and 1.30 ± 0.29 pg/ml in CD ETA KO mice). CD ETA KO mice had a modestly enhanced ability to excrete an acute, but not a chronic, water load. DDAVP infusion increased Uosm similarly; however, CD ETA KO mice had a more rapid subsequent fall in Uosm during sustained DDAVP administration. CD suspensions from CD ETA KO mice had a 30-40% reduction in AVP- and forskolin-stimulated cAMP accumulation. These data indicate that CD ETA KO decreases renal sensitivity to the urinary concentrating effects of AVP and suggest that activation of the ETA receptor downregulates ET-1 inhibition of AVP actions in the CD. Furthermore, the CD ETA receptor does not appear to be involved in modulation of systemic blood pressure or renal Na excretion under physiological conditions.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume289
Issue number4 58-4
DOIs
StatePublished - Oct 2005

Fingerprint

Endothelin A Receptors
Vasopressins
Knockout Mice
Sodium
Osmolar Concentration
Blood Pressure
Kidney
Deamino Arginine Vasopressin
Endothelin-1
Nephrons
Colforsin
Aldosterone
Renin
Drinking
Suspensions
Down-Regulation
Diet
Hypertension
Water
Genes

Keywords

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

ASJC Scopus subject areas

  • Physiology

Cite this

Collecting duct-specific knockout of the endothelin A receptor alters renal vasopressin responsiveness, but not sodium excretion or blood pressure. / Ge, Yuqiang; Stricklett, Peter K.; Hughes, Alisa K.; Yanagisawa, Masashi; Kohan, Donald E.

In: American Journal of Physiology - Renal Physiology, Vol. 289, No. 4 58-4, 10.2005.

Research output: Contribution to journalArticle

@article{b4303c6f7fce4b70889d330f41348a33,
title = "Collecting duct-specific knockout of the endothelin A receptor alters renal vasopressin responsiveness, but not sodium excretion or blood pressure",
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, ETA and ETB; in the current study, the role of the CD ETA receptor in mediating ET-1 actions on this nephron segment was evaluated. The ETA receptor gene was selectively disrupted in CD (CD ETA KO). CD ETA 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 ETA KO animals (0.57 ± 0.25 pg/ml in controls and 1.30 ± 0.29 pg/ml in CD ETA KO mice). CD ETA KO mice had a modestly enhanced ability to excrete an acute, but not a chronic, water load. DDAVP infusion increased Uosm similarly; however, CD ETA KO mice had a more rapid subsequent fall in Uosm during sustained DDAVP administration. CD suspensions from CD ETA KO mice had a 30-40{\%} reduction in AVP- and forskolin-stimulated cAMP accumulation. These data indicate that CD ETA KO decreases renal sensitivity to the urinary concentrating effects of AVP and suggest that activation of the ETA receptor downregulates ET-1 inhibition of AVP actions in the CD. Furthermore, the CD ETA receptor does not appear to be involved in modulation of systemic blood pressure or renal Na excretion under physiological conditions.",
keywords = "Adenosine 3′,5′-cyclic monophosphate, Inner medullary collecting duct, Tubule",
author = "Yuqiang Ge and Stricklett, {Peter K.} and Hughes, {Alisa K.} and Masashi Yanagisawa and Kohan, {Donald E.}",
year = "2005",
month = "10",
doi = "10.1152/ajprenal.00100.2005",
language = "English (US)",
volume = "289",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "4 58-4",

}

TY - JOUR

T1 - Collecting duct-specific knockout of the endothelin A receptor alters renal vasopressin responsiveness, but not sodium excretion or blood pressure

AU - Ge, Yuqiang

AU - Stricklett, Peter K.

AU - Hughes, Alisa K.

AU - Yanagisawa, Masashi

AU - Kohan, Donald E.

PY - 2005/10

Y1 - 2005/10

N2 - 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, ETA and ETB; in the current study, the role of the CD ETA receptor in mediating ET-1 actions on this nephron segment was evaluated. The ETA receptor gene was selectively disrupted in CD (CD ETA KO). CD ETA 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 ETA KO animals (0.57 ± 0.25 pg/ml in controls and 1.30 ± 0.29 pg/ml in CD ETA KO mice). CD ETA KO mice had a modestly enhanced ability to excrete an acute, but not a chronic, water load. DDAVP infusion increased Uosm similarly; however, CD ETA KO mice had a more rapid subsequent fall in Uosm during sustained DDAVP administration. CD suspensions from CD ETA KO mice had a 30-40% reduction in AVP- and forskolin-stimulated cAMP accumulation. These data indicate that CD ETA KO decreases renal sensitivity to the urinary concentrating effects of AVP and suggest that activation of the ETA receptor downregulates ET-1 inhibition of AVP actions in the CD. Furthermore, the CD ETA receptor does not appear to be involved in modulation of systemic blood pressure or renal Na excretion under physiological conditions.

AB - 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, ETA and ETB; in the current study, the role of the CD ETA receptor in mediating ET-1 actions on this nephron segment was evaluated. The ETA receptor gene was selectively disrupted in CD (CD ETA KO). CD ETA 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 ETA KO animals (0.57 ± 0.25 pg/ml in controls and 1.30 ± 0.29 pg/ml in CD ETA KO mice). CD ETA KO mice had a modestly enhanced ability to excrete an acute, but not a chronic, water load. DDAVP infusion increased Uosm similarly; however, CD ETA KO mice had a more rapid subsequent fall in Uosm during sustained DDAVP administration. CD suspensions from CD ETA KO mice had a 30-40% reduction in AVP- and forskolin-stimulated cAMP accumulation. These data indicate that CD ETA KO decreases renal sensitivity to the urinary concentrating effects of AVP and suggest that activation of the ETA receptor downregulates ET-1 inhibition of AVP actions in the CD. Furthermore, the CD ETA receptor does not appear to be involved in modulation of systemic blood pressure or renal Na excretion under physiological conditions.

KW - Adenosine 3′,5′-cyclic monophosphate

KW - Inner medullary collecting duct

KW - Tubule

UR - http://www.scopus.com/inward/record.url?scp=24944554452&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=24944554452&partnerID=8YFLogxK

U2 - 10.1152/ajprenal.00100.2005

DO - 10.1152/ajprenal.00100.2005

M3 - Article

C2 - 15928212

AN - SCOPUS:24944554452

VL - 289

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 4 58-4

ER -