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

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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

All Science Journal Classification (ASJC) codes

  • Nephrology

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    Giani, J. F., Eriguchi, M., Bernstein, E. A., Katsumata, M., Shen, X. Z., Li, L., McDonough, A. A., Fuchs, S., Bernstein, K. E., & 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