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ET-1 increases reactive oxygen species following hypoxia and high-salt diet in the mouse glomerulus.
- Source :
-
Acta physiologica (Oxford, England) [Acta Physiol (Oxf)] 2015 Mar; Vol. 213 (3), pp. 722-30. Date of Electronic Publication: 2014 Sep 29. - Publication Year :
- 2015
-
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.<br />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).<br />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.<br />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.<br /> (© 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)
- Subjects :
- Animals
Disease Models, Animal
Endothelin A Receptor Antagonists pharmacology
Endothelin-1 deficiency
Endothelin-1 genetics
Hypoxia complications
Kidney Diseases etiology
Kidney Diseases genetics
Kidney Diseases physiopathology
Kidney Glomerulus drug effects
Kidney Glomerulus physiopathology
Male
Mice, Inbred C57BL
Mice, Knockout
Proteinuria metabolism
Proteinuria physiopathology
Receptor, Endothelin A drug effects
Receptor, Endothelin A metabolism
Sodium Chloride, Dietary metabolism
Time Factors
Endothelin-1 administration & dosage
Hypoxia metabolism
Kidney Diseases metabolism
Kidney Glomerulus metabolism
Oxidative Stress drug effects
Reactive Oxygen Species metabolism
Sodium Chloride, Dietary adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 1748-1716
- Volume :
- 213
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Acta physiologica (Oxford, England)
- Publication Type :
- Academic Journal
- Accession number :
- 25219340
- Full Text :
- https://doi.org/10.1111/apha.12397