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Endothelin‐1 and the Recovery of Renal Perfusion Post‐Ischemia
Author(s) -
Boesen Erika
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.807.2
Subject(s) - kidney , medicine , perfusion , ischemia , endothelin receptor , renal circulation , urology , blockade , kidney disease , hypoxia (environmental) , acute kidney injury , endothelin 1 , endocrinology , anesthesia , cardiology , renal blood flow , receptor , chemistry , organic chemistry , oxygen
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 ET A receptor blockade (ABT‐627) or endothelial cell deletion of ET‐1 (EC ET‐1 ‐/‐ ), would improve recovery of renal perfusion and repair of injury following a severe ischemic insult (45 min unilateral renal ischemia). Male C57Bl/6 mice receiving vehicle or ABT‐627 (10 mg/kg/d p.o.) commencing 2 days prior to surgery, and EC ET‐1 ‐/‐ mice and wild‐type littermates (WT) underwent 45 min unilateral renal IR surgery followed by 28 days recovery. Peak systolic renal blood velocity (RBV) was measured by pulsed wave Doppler ultrasound before and after surgery. RBV was not significantly different between pairs of groups before surgery. Unilateral IR induced a marked reduction in RBV of the IR kidney at 24 hours post‐surgery in all groups (Table), which partially recovered but remained below baseline at 28 days post‐IR. Despite the lack of effect on perfusion, ET A receptor blockade significantly attenuated the atrophy of the IR kidney, whereas this was not significantly affected by lack of endothelial ET‐1 expression. These data suggest that although blockade of the ET A receptor is beneficial in preserving renal mass following a severe ischemic insult, this protective effect does not appear to involve improved recovery of renal perfusion.RBV at 24h (% baseline) RBV at 28d (% baseline) IR Kidney (mg) Contralateral Kidney (mg) IR:Contralateral Kidney Ratio Vehicle (n=5) 44±6* 47±11* 64±3 213±5 0.30±0.01 ABT‐627 (n=6) 52±5* 61±4* 89±6# 211±4 0.42±0.03# WT (n=6) 24±3* 61±6* 48±3 188±8 0.25±0.01 EC ET‐1 ‐/‐ (n=6) 34±6* 69±12* 64±9 200±10 0.32±0.03*P<0.01 vs baseline; #P<0.01 vs respective control group