Lack of an apparent role for endothelin-1 in the prolonged reduction in renal perfusion following severe unilateral ischemia-reperfusion injury in the mouse

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4 Scopus citations

Abstract

Therapeutic approaches to block the progression from acute kidney injury to chronic kidney disease are currently lacking. Endothelin-1 (ET-1) is a powerful vasoconstrictor, induced by hypoxia, and previously implicated in renal ischemia-reperfusion (IR) injury. This study tested the hypothesis that blunting the vascular influence of ET-1, either through endothelin ETA receptor blockade (ABT-627) or vascular endothelial cell deletion of ET-1 (VEET KO), would improve recovery of renal perfusion and repair of injury following a severe ischemic insult in mice (45 min unilateral renal ischemia). Male C57Bl/6 mice receiving vehicle or ABT-627 commencing 2 days prior to surgery, and VEET KO mice and wild-type littermates (WT) underwent 45 min unilateral renal IR surgery followed by 28 days recovery. Renal blood velocity was measured by pulsed-wave Doppler ultrasound before and after surgery. Renal blood velocity was not significantly different between pairs of groups before surgery. Unilateral IR induced a marked reduction in renal blood velocity of the IR kidney at 24 h postsurgery in all groups, which partially recovered but remained below baseline at 28 days post-IR. Despite the lack of effect on renal blood velocity, ETA receptor blockade significantly attenuated the atrophy of the post-IR kidney, whereas this was not significantly affected by lack of endothelial ET-1 expression. These data suggest that although blockade of the ETA receptor is mildly beneficial in preserving renal mass following a severe ischemic insult, this protective effect does not appear to involve improved recovery of renal perfusion.

Original languageEnglish (US)
Article numbere13027
JournalPhysiological Reports
Volume4
Issue number21
DOIs
StatePublished - Nov 1 2016

Keywords

  • Endothelin-1
  • Ischemia
  • Kidney
  • Renal perfusion
  • Ultrasound

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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