In:
Acta Physiologica, Wiley, Vol. 213, No. 3 ( 2015-03), p. 722-730
Abstract:
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 BL 6/J control mice or vascular endothelial cell ET ‐1 knockout ( VEET KO ) mice were subjected to 3‐h exposure to hypoxia (8% O 2 ) 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 ET A 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 ET A antagonist treatment. Conclusion These data suggest that both hypoxia and a high‐salt diet increase glomerular ROS production via endothelial‐derived ET ‐1‐ ET A receptor activation and provide a potential mechanism for ET ‐1‐induced nephropathy.
Type of Medium:
Online Resource
ISSN:
1748-1708
,
1748-1716
DOI:
10.1111/apha.2015.213.issue-3
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2617148-X
detail.hit.zdb_id:
2219379-0
SSG:
12
Bookmarklink