Renal tubular angiotensin converting enzyme is responsible for nitro-L-arginine methyl ester (L-NAME)-induced salt sensitivity

Jorge F. Giani, Masahiro Eriguchi, Ellen A. Bernstein, Makoto Katsumata, Xiao Z. Shen, Liang Li, Alicia A. McDonough, Sebastien Fuchs, Kenneth E. Bernstein, Romer A. Gonzalez-Villalobos

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Renal parenchymal injury predisposes to salt-sensitive hypertension, but how this occurs is not known. Here we tested whether renal tubular angiotensin converting enzyme (ACE), the main site of kidney ACE expression, is central to the development of salt sensitivity in this setting. Two mouse models were used: it-ACE mice in which ACE expression is selectively eliminated from renal tubular epithelial cells; and ACE 3/9 mice, a compound heterozygous mouse model that makes ACE only in renal tubular epithelium from the ACE 9 allele, and in liver hepatocytes from the ACE 3 allele. Salt sensitivity was induced using a post L-NAME salt challenge. While both wild-type and ACE 3/9 mice developed arterial hypertension following three weeks of high salt administration, it-ACE mice remained normotensive with low levels of renal angiotensin II. These mice displayed increased sodium excretion, lower sodium accumulation, and an exaggerated reduction in distal sodium transporters. Thus, in mice with renal injury induced by L-NAME pretreatment, renal tubular epithelial ACE, and not ACE expression by renal endothelium, lung, brain, or plasma, is essential for renal angiotensin II accumulation and salt-sensitive hypertension.

Original languageEnglish
Pages (from-to)856-867
Number of pages12
JournalKidney International
Volume91
Issue number4
DOIs
Publication statusPublished - Apr 1 2017

Fingerprint

NG-Nitroarginine Methyl Ester
Peptidyl-Dipeptidase A
Salts
Kidney
Sodium
Hypertension
Angiotensin II
Alleles
arginine methyl ester
Wounds and Injuries
Endothelium
Hepatocytes
Epithelium
Epithelial Cells
Lung
Liver

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Giani, J. F., Eriguchi, M., Bernstein, E. A., Katsumata, M., Shen, X. Z., Li, L., ... Gonzalez-Villalobos, R. A. (2017). Renal tubular angiotensin converting enzyme is responsible for nitro-L-arginine methyl ester (L-NAME)-induced salt sensitivity. Kidney International, 91(4), 856-867. https://doi.org/10.1016/j.kint.2016.10.007

Renal tubular angiotensin converting enzyme is responsible for nitro-L-arginine methyl ester (L-NAME)-induced salt sensitivity. / Giani, Jorge F.; Eriguchi, Masahiro; Bernstein, Ellen A.; Katsumata, Makoto; Shen, Xiao Z.; Li, Liang; McDonough, Alicia A.; Fuchs, Sebastien; Bernstein, Kenneth E.; Gonzalez-Villalobos, Romer A.

In: Kidney International, Vol. 91, No. 4, 01.04.2017, p. 856-867.

Research output: Contribution to journalArticle

Giani, JF, Eriguchi, M, Bernstein, EA, Katsumata, M, Shen, XZ, Li, L, McDonough, AA, Fuchs, S, Bernstein, KE & Gonzalez-Villalobos, RA 2017, 'Renal tubular angiotensin converting enzyme is responsible for nitro-L-arginine methyl ester (L-NAME)-induced salt sensitivity', Kidney International, vol. 91, no. 4, pp. 856-867. https://doi.org/10.1016/j.kint.2016.10.007
Giani, Jorge F. ; Eriguchi, Masahiro ; Bernstein, Ellen A. ; Katsumata, Makoto ; Shen, Xiao Z. ; Li, Liang ; McDonough, Alicia A. ; Fuchs, Sebastien ; Bernstein, Kenneth E. ; Gonzalez-Villalobos, Romer A. / Renal tubular angiotensin converting enzyme is responsible for nitro-L-arginine methyl ester (L-NAME)-induced salt sensitivity. In: Kidney International. 2017 ; Vol. 91, No. 4. pp. 856-867.
@article{5b9deead31aa4efc868447c016d6715f,
title = "Renal tubular angiotensin converting enzyme is responsible for nitro-L-arginine methyl ester (L-NAME)-induced salt sensitivity",
abstract = "Renal parenchymal injury predisposes to salt-sensitive hypertension, but how this occurs is not known. Here we tested whether renal tubular angiotensin converting enzyme (ACE), the main site of kidney ACE expression, is central to the development of salt sensitivity in this setting. Two mouse models were used: it-ACE mice in which ACE expression is selectively eliminated from renal tubular epithelial cells; and ACE 3/9 mice, a compound heterozygous mouse model that makes ACE only in renal tubular epithelium from the ACE 9 allele, and in liver hepatocytes from the ACE 3 allele. Salt sensitivity was induced using a post L-NAME salt challenge. While both wild-type and ACE 3/9 mice developed arterial hypertension following three weeks of high salt administration, it-ACE mice remained normotensive with low levels of renal angiotensin II. These mice displayed increased sodium excretion, lower sodium accumulation, and an exaggerated reduction in distal sodium transporters. Thus, in mice with renal injury induced by L-NAME pretreatment, renal tubular epithelial ACE, and not ACE expression by renal endothelium, lung, brain, or plasma, is essential for renal angiotensin II accumulation and salt-sensitive hypertension.",
author = "Giani, {Jorge F.} and Masahiro Eriguchi and Bernstein, {Ellen A.} and Makoto Katsumata and Shen, {Xiao Z.} and Liang Li and McDonough, {Alicia A.} and Sebastien Fuchs and Bernstein, {Kenneth E.} and Gonzalez-Villalobos, {Romer A.}",
year = "2017",
month = "4",
day = "1",
doi = "10.1016/j.kint.2016.10.007",
language = "English",
volume = "91",
pages = "856--867",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Renal tubular angiotensin converting enzyme is responsible for nitro-L-arginine methyl ester (L-NAME)-induced salt sensitivity

AU - Giani, Jorge F.

AU - Eriguchi, Masahiro

AU - Bernstein, Ellen A.

AU - Katsumata, Makoto

AU - Shen, Xiao Z.

AU - Li, Liang

AU - McDonough, Alicia A.

AU - Fuchs, Sebastien

AU - Bernstein, Kenneth E.

AU - Gonzalez-Villalobos, Romer A.

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Renal parenchymal injury predisposes to salt-sensitive hypertension, but how this occurs is not known. Here we tested whether renal tubular angiotensin converting enzyme (ACE), the main site of kidney ACE expression, is central to the development of salt sensitivity in this setting. Two mouse models were used: it-ACE mice in which ACE expression is selectively eliminated from renal tubular epithelial cells; and ACE 3/9 mice, a compound heterozygous mouse model that makes ACE only in renal tubular epithelium from the ACE 9 allele, and in liver hepatocytes from the ACE 3 allele. Salt sensitivity was induced using a post L-NAME salt challenge. While both wild-type and ACE 3/9 mice developed arterial hypertension following three weeks of high salt administration, it-ACE mice remained normotensive with low levels of renal angiotensin II. These mice displayed increased sodium excretion, lower sodium accumulation, and an exaggerated reduction in distal sodium transporters. Thus, in mice with renal injury induced by L-NAME pretreatment, renal tubular epithelial ACE, and not ACE expression by renal endothelium, lung, brain, or plasma, is essential for renal angiotensin II accumulation and salt-sensitive hypertension.

AB - Renal parenchymal injury predisposes to salt-sensitive hypertension, but how this occurs is not known. Here we tested whether renal tubular angiotensin converting enzyme (ACE), the main site of kidney ACE expression, is central to the development of salt sensitivity in this setting. Two mouse models were used: it-ACE mice in which ACE expression is selectively eliminated from renal tubular epithelial cells; and ACE 3/9 mice, a compound heterozygous mouse model that makes ACE only in renal tubular epithelium from the ACE 9 allele, and in liver hepatocytes from the ACE 3 allele. Salt sensitivity was induced using a post L-NAME salt challenge. While both wild-type and ACE 3/9 mice developed arterial hypertension following three weeks of high salt administration, it-ACE mice remained normotensive with low levels of renal angiotensin II. These mice displayed increased sodium excretion, lower sodium accumulation, and an exaggerated reduction in distal sodium transporters. Thus, in mice with renal injury induced by L-NAME pretreatment, renal tubular epithelial ACE, and not ACE expression by renal endothelium, lung, brain, or plasma, is essential for renal angiotensin II accumulation and salt-sensitive hypertension.

UR - http://www.scopus.com/inward/record.url?scp=85008354901&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85008354901&partnerID=8YFLogxK

U2 - 10.1016/j.kint.2016.10.007

DO - 10.1016/j.kint.2016.10.007

M3 - Article

C2 - 27988209

AN - SCOPUS:85008354901

VL - 91

SP - 856

EP - 867

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 4

ER -