Lack of an effect of collecting duct-specific deletion of adenylyl cyclase 3 on renal Na+ and water excretion or arterial pressure

Wararat Kittikulsuth, Deborah Stuart, Alfred N. Van Hoek, James D Stockand, Vladislav Bugaj, Elena Mironova, Mitsi A. Blount, Donald E. Kohan

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

CAMP is a key mediator of connecting tubule and collecting duct (CD) Na+ and water reabsorption. Studies performed in vitro have suggested that CD adenylyl cyclase (AC)3 partly mediates the actions of vasopressin; however, the physiological role of CD AC3 has not been determined. To assess this, mice were developed with CD-specific disruption of AC3 [CD AC3 knockout (KO)]. Inner medullary CDs from these mice exhibited 100% target gene recombination and had reduced ANG II- but not vasopressin-induced cAMP accumulation. However, there were no differences in urine volume, urinary urea excretion, or urine osmolality between KO and control mice during normal water intake or varying degrees of water restriction in the presence or absence of chronic vasopressin administration. There were no differences between CD AC3 KO and control mice in arterial pressure or urinary Na+ or K+ excretion during a normal or high-salt diet, whereas plasma renin and vasopressin concentrations were similar between the two genotypes. Patch-clamp analysis of split-open cortical CDs revealed no difference in epithelial Na+ channel activity in the presence or absence of vasopressin. Compensatory changes in AC6 were not responsible for the lack of a renal phenotype in CD AC3 KO mice since combined CD AC3/AC6 KO mice had similar arterial pressure and renal Na+ and water handling compared with CD AC6 KO mice. In summary, these data do not support a significant role for CD AC3 in the regulation of renal Na+ and water excretion in general or vasopressin regulation of CD function in particular.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume306
Issue number6
DOIs
StatePublished - Mar 15 2014

Fingerprint

Vasopressins
Adenylyl Cyclases
Arterial Pressure
Knockout Mice
Kidney
Water
Urine
Epithelial Sodium Channels
Renin
Osmolar Concentration
Genetic Recombination
Drinking
Urea
Salts
Genotype
Diet
Phenotype
Genes

Keywords

  • Adenylyl cyclase 3
  • Blood pressure
  • Collecting duct
  • Gene targeting
  • Urinary sodium and water excretion

ASJC Scopus subject areas

  • Physiology
  • Urology
  • Medicine(all)

Cite this

Lack of an effect of collecting duct-specific deletion of adenylyl cyclase 3 on renal Na+ and water excretion or arterial pressure. / Kittikulsuth, Wararat; Stuart, Deborah; Van Hoek, Alfred N.; Stockand, James D; Bugaj, Vladislav; Mironova, Elena; Blount, Mitsi A.; Kohan, Donald E.

In: American Journal of Physiology - Renal Physiology, Vol. 306, No. 6, 15.03.2014.

Research output: Contribution to journalArticle

Kittikulsuth, Wararat ; Stuart, Deborah ; Van Hoek, Alfred N. ; Stockand, James D ; Bugaj, Vladislav ; Mironova, Elena ; Blount, Mitsi A. ; Kohan, Donald E. / Lack of an effect of collecting duct-specific deletion of adenylyl cyclase 3 on renal Na+ and water excretion or arterial pressure. In: American Journal of Physiology - Renal Physiology. 2014 ; Vol. 306, No. 6.
@article{31858227ba2f4f5f9fb0d8b480a78e32,
title = "Lack of an effect of collecting duct-specific deletion of adenylyl cyclase 3 on renal Na+ and water excretion or arterial pressure",
abstract = "CAMP is a key mediator of connecting tubule and collecting duct (CD) Na+ and water reabsorption. Studies performed in vitro have suggested that CD adenylyl cyclase (AC)3 partly mediates the actions of vasopressin; however, the physiological role of CD AC3 has not been determined. To assess this, mice were developed with CD-specific disruption of AC3 [CD AC3 knockout (KO)]. Inner medullary CDs from these mice exhibited 100{\%} target gene recombination and had reduced ANG II- but not vasopressin-induced cAMP accumulation. However, there were no differences in urine volume, urinary urea excretion, or urine osmolality between KO and control mice during normal water intake or varying degrees of water restriction in the presence or absence of chronic vasopressin administration. There were no differences between CD AC3 KO and control mice in arterial pressure or urinary Na+ or K+ excretion during a normal or high-salt diet, whereas plasma renin and vasopressin concentrations were similar between the two genotypes. Patch-clamp analysis of split-open cortical CDs revealed no difference in epithelial Na+ channel activity in the presence or absence of vasopressin. Compensatory changes in AC6 were not responsible for the lack of a renal phenotype in CD AC3 KO mice since combined CD AC3/AC6 KO mice had similar arterial pressure and renal Na+ and water handling compared with CD AC6 KO mice. In summary, these data do not support a significant role for CD AC3 in the regulation of renal Na+ and water excretion in general or vasopressin regulation of CD function in particular.",
keywords = "Adenylyl cyclase 3, Blood pressure, Collecting duct, Gene targeting, Urinary sodium and water excretion",
author = "Wararat Kittikulsuth and Deborah Stuart and {Van Hoek}, {Alfred N.} and Stockand, {James D} and Vladislav Bugaj and Elena Mironova and Blount, {Mitsi A.} and Kohan, {Donald E.}",
year = "2014",
month = "3",
day = "15",
doi = "10.1152/ajprenal.00505.2013",
language = "English (US)",
volume = "306",
journal = "American Journal of Physiology - Renal Physiology",
issn = "0363-6127",
publisher = "American Physiological Society",
number = "6",

}

TY - JOUR

T1 - Lack of an effect of collecting duct-specific deletion of adenylyl cyclase 3 on renal Na+ and water excretion or arterial pressure

AU - Kittikulsuth, Wararat

AU - Stuart, Deborah

AU - Van Hoek, Alfred N.

AU - Stockand, James D

AU - Bugaj, Vladislav

AU - Mironova, Elena

AU - Blount, Mitsi A.

AU - Kohan, Donald E.

PY - 2014/3/15

Y1 - 2014/3/15

N2 - CAMP is a key mediator of connecting tubule and collecting duct (CD) Na+ and water reabsorption. Studies performed in vitro have suggested that CD adenylyl cyclase (AC)3 partly mediates the actions of vasopressin; however, the physiological role of CD AC3 has not been determined. To assess this, mice were developed with CD-specific disruption of AC3 [CD AC3 knockout (KO)]. Inner medullary CDs from these mice exhibited 100% target gene recombination and had reduced ANG II- but not vasopressin-induced cAMP accumulation. However, there were no differences in urine volume, urinary urea excretion, or urine osmolality between KO and control mice during normal water intake or varying degrees of water restriction in the presence or absence of chronic vasopressin administration. There were no differences between CD AC3 KO and control mice in arterial pressure or urinary Na+ or K+ excretion during a normal or high-salt diet, whereas plasma renin and vasopressin concentrations were similar between the two genotypes. Patch-clamp analysis of split-open cortical CDs revealed no difference in epithelial Na+ channel activity in the presence or absence of vasopressin. Compensatory changes in AC6 were not responsible for the lack of a renal phenotype in CD AC3 KO mice since combined CD AC3/AC6 KO mice had similar arterial pressure and renal Na+ and water handling compared with CD AC6 KO mice. In summary, these data do not support a significant role for CD AC3 in the regulation of renal Na+ and water excretion in general or vasopressin regulation of CD function in particular.

AB - CAMP is a key mediator of connecting tubule and collecting duct (CD) Na+ and water reabsorption. Studies performed in vitro have suggested that CD adenylyl cyclase (AC)3 partly mediates the actions of vasopressin; however, the physiological role of CD AC3 has not been determined. To assess this, mice were developed with CD-specific disruption of AC3 [CD AC3 knockout (KO)]. Inner medullary CDs from these mice exhibited 100% target gene recombination and had reduced ANG II- but not vasopressin-induced cAMP accumulation. However, there were no differences in urine volume, urinary urea excretion, or urine osmolality between KO and control mice during normal water intake or varying degrees of water restriction in the presence or absence of chronic vasopressin administration. There were no differences between CD AC3 KO and control mice in arterial pressure or urinary Na+ or K+ excretion during a normal or high-salt diet, whereas plasma renin and vasopressin concentrations were similar between the two genotypes. Patch-clamp analysis of split-open cortical CDs revealed no difference in epithelial Na+ channel activity in the presence or absence of vasopressin. Compensatory changes in AC6 were not responsible for the lack of a renal phenotype in CD AC3 KO mice since combined CD AC3/AC6 KO mice had similar arterial pressure and renal Na+ and water handling compared with CD AC6 KO mice. In summary, these data do not support a significant role for CD AC3 in the regulation of renal Na+ and water excretion in general or vasopressin regulation of CD function in particular.

KW - Adenylyl cyclase 3

KW - Blood pressure

KW - Collecting duct

KW - Gene targeting

KW - Urinary sodium and water excretion

UR - http://www.scopus.com/inward/record.url?scp=84900332894&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84900332894&partnerID=8YFLogxK

U2 - 10.1152/ajprenal.00505.2013

DO - 10.1152/ajprenal.00505.2013

M3 - Article

C2 - 24431204

AN - SCOPUS:84900332894

VL - 306

JO - American Journal of Physiology - Renal Physiology

JF - American Journal of Physiology - Renal Physiology

SN - 0363-6127

IS - 6

ER -