Thromboxane receptor signalling in renal ischemia reperfusion injury

Abstract

F₂-isoprostanes are formed by oxidative modification of arachidonic acid and are the gold standard for detection of oxidative stress in vivo. F₂-isoprostanes are biologically active compounds that signal through the thromboxane A₂ (TP) receptor; infusion of F₂-isoprostanes reduces glomerular filtration in the kidney by constricting afferent arterioles. This study investigated whether endogenous F₂-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 F₂-isoprostanes and thromboxane A₂ 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. F₂-isoprostanes and thromboxane B₂ were readily detectable in urine collections after surgery. The findings indicate that F₂-isoprostanes and thromboxane A₂ signalling do not contribute critically to the pathogenesis of ischemic acute kidney injury and more generally provide evidence against a prominent role for F₂-isoprostanes signalling in exacerbating acute disease states associated with oxidative stress.

Keywords::

• Acute kidney injury
• F₂-isoprostanes
• ischemia reperfusion injury
• thromboxane A₂
• TP receptor

This paper was first published online on Early Online 7 April 2011.