Thromboxane receptor signalling in renal ischemia reperfusion injury.

Published

Journal Article

F(2)-isoprostanes are formed by oxidative modification of arachidonic acid and are the gold standard for detection of oxidative stress in vivo. F(2)-isoprostanes are biologically active compounds that signal through the thromboxane A(2) (TP) receptor; infusion of F(2)-isoprostanes reduces glomerular filtration in the kidney by constricting afferent arterioles. This study investigated whether endogenous F(2)-isoprostanes contribute to the pathogenesis of ischemic acute kidney injury, which is associated with oxidative stress and reduced glomerular filtration. TP receptor knockout mice-that lack F(2)-isoprostanes and thromboxane A(2) signalling-and wild-type control mice underwent 30 min of renal ischemia and 24 h of reperfusion. Kidney dysfunction, histological injury and the number of infiltrated neutrophils were similar between the two mouse strains, whereas TP receptor knockout mice had significantly more apoptotic cells and tissue lipid peroxidation than their wild-type counterparts. F(2)-isoprostanes and thromboxane B(2) were readily detectable in urine collections after surgery. The findings indicate that F(2)-isoprostanes and thromboxane A(2) signalling do not contribute critically to the pathogenesis of ischemic acute kidney injury and more generally provide evidence against a prominent role for F(2)-isoprostanes signalling in exacerbating acute disease states associated with oxidative stress.

Full Text

Duke Authors

Cited Authors

  • Snoeijs, MGJ; Hoogland, PR; Boonen, B; Coffman, TM; Peutz-Kootstra, CJ; Buurman, WA; van Heurn, LWE

Published Date

  • June 2011

Published In

Volume / Issue

  • 45 / 6

Start / End Page

  • 699 - 706

PubMed ID

  • 21449636

Pubmed Central ID

  • 21449636

Electronic International Standard Serial Number (EISSN)

  • 1029-2470

Digital Object Identifier (DOI)

  • 10.3109/10715762.2011.571686

Language

  • eng

Conference Location

  • England