ET-1 increases reactive oxygen species following hypoxia and high-salt diet in the mouse glomerulus

J. B. Heimlich, J. S. Speed, C. J. Bloom, P. M. O'Connor, J. S. Pollock, D. M. Pollock

Research output: Contribution to journalEditorial

24 Scopus citations

Abstract

Aim: This study was designed to determine whether ET-1 derived from endothelial cells contributes to oxidative stress in the glomerulus of mice subjected to a high-salt diet and/or hypoxia. Methods: C57BL6/J control mice or vascular endothelial cell ET-1 knockout (VEET KO) mice were subjected to 3-h exposure to hypoxia (8% O2) and/or 2 weeks of high-salt diet (4% NaCl) prior to metabolic cage assessment of renal function and isolation of glomeruli for the determination of reactive oxygen species (ROS). Results: In control mice, hypoxia significantly increased urinary protein excretion during the initial 24 h, but only in animals on a high-salt diet. Hypoxia increased glomerular ET-1 mRNA expression in control, but not in vascular endothelial cell ET-1 knockout (VEET KO) mice. Under normoxic conditions, mice on a high-salt diet had approx. 150% higher glomerular ET-1 mRNA expression compared with a normal-salt diet (P < 0.05). High-salt diet administration significantly increased glomerular ROS production in flox control, but not in glomeruli isolated from VEET KO mice. In C57BL6/J mice, the ETA receptor-selective antagonist, ABT-627, significantly attenuated the increase in glomerular ROS production produced by high-salt diet. In addition, chronic infusion of C57BL6/J mice with a subpressor dose of ET-1 (osmotic pumps) significantly increased the levels of glomerular ROS that were prevented by ETA antagonist treatment. Conclusion: These data suggest that both hypoxia and a high-salt diet increase glomerular ROS production via endothelial-derived ET-1-ETA receptor activation and provide a potential mechanism for ET-1-induced nephropathy.

Original languageEnglish (US)
Pages (from-to)722-730
Number of pages9
JournalActa Physiologica
Volume213
Issue number3
DOIs
StatePublished - Mar 1 2015

Keywords

  • Endothelin
  • Glomerulus
  • High-salt diet
  • Hypoxia
  • Kidney
  • Reactive oxygen species

ASJC Scopus subject areas

  • Physiology

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