ET-1 increases reactive oxygen species following hypoxia and high-salt diet in the mouse glomerulus.
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| Title: | ET-1 increases reactive oxygen species following hypoxia and high-salt diet in the mouse glomerulus. |
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| Authors: | Heimlich, J. B., Speed, J. S., Bloom, C. J., O'Connor, P. M., Pollock, J. S., Pollock, D. M. |
| Source: | Acta Physiologica. Mar2015, Vol. 213 Issue 3, p722-730. 9p. 7 Graphs. |
| Subjects: | Oxidative stress, Kidney glomerulus, Vascular endothelial cells, Hypoxemia, High-salt diet, Mice physiology, Laboratory mice |
| 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 C57 BL6/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. [ABSTRACT FROM AUTHOR] |
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| Database: | Psychology and Behavioral Sciences Collection |
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| 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 C57 BL6/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. [ABSTRACT FROM AUTHOR] |
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| ISSN: | 17481708 |
| DOI: | 10.1111/apha.12397 |
