Article

Protective effect of 20-HETE analogues in experimental renal ischemia reperfusion injury.

Department of Nephrology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Kidney International (impact factor: 6.61). 01/2009; 75(5):511-7. DOI:10.1038/ki.2008.600 pp.511-7
Source: PubMed

ABSTRACT While it is known that the arachidonic acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) contributes to ischemic injury in the heart and brain, its role in kidney injury is unclear. Here we determined the effects on ischemia-reperfusion injury of the 20-HETE analogues, 20-hydroxyeicosa-5(Z), 14(Z)-dienoic acid (5,14-20-HEDE), and N-[20-hydroxyeicosa-5(Z),14(Z)-dienoyl]glycine (5,14-20-HEDGE), and of the inhibitor of 20-HETE synthesis N-hydroxy-N-(4-butyl-2 methylphenyl) formamidine (HET0016). Using Sprague-Dawley rats we found that while treatment with the inhibitor exacerbated renal injury, infusion of both 5,14-20-HEDE and 5,14-20-HEDGE significantly attenuated injury when compared to vehicle or inhibitor-treated rats. Medullary blood flow, measured by laser-Doppler flowmetry, decreased to half of the baseline one hour after reperfusion in the control rats, but 5,14-20-HEDGE completely prevented this. Treatment of control animals with 5,14-20-HEDGE increased urine output and sodium excretion without altering their mean arterial pressure or glomerular filtration rate. Our results suggest that 20-HETE analogues protect the kidney from ischemia-reperfusion injury by inhibiting renal tubular sodium transport and preventing the post-ischemic fall in medullary blood flow. Analogues of 20-HETE may be useful in the treatment of acute ischemic kidney injury.

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Keywords

20-HETE analogues
 
20-HETE synthesis N-hydroxy-N-(4-butyl-2 methylphenyl)
 
20-hydroxyeicosa-5(Z)
 
control animals
 
control rats
 
glomerular filtration rate
 
infusion
 
inhibiting renal tubular sodium transport
 
inhibitor exacerbated renal injury
 
inhibitor-treated rats
 
ischemia-reperfusion injury
 
laser-Doppler flowmetry
 
mean arterial pressure
 
Medullary blood flow
 
post-ischemic fall
 
sodium excretion
 
Sprague-Dawley rats
 
urine output