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Protective effect of 20-HETE analogues in experimental renal ischemia reperfusion injury. Kidney Int 2009 Mar;75(5):511-7

Date

12/05/2008

Pubmed ID

19052533

Pubmed Central ID

PMC2643317

DOI

10.1038/ki.2008.600

Scopus ID

2-s2.0-60749108287   68 Citations

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.

Author List

Regner KR, Zuk A, Van Why SK, Shames BD, Ryan RP, Falck JR, Manthati VL, McMullen ME, Ledbetter SR, Roman RJ

Authors

Kevin R. Regner MD Chief, Professor in the Medicine department at Medical College of Wisconsin
Scott K. Van Why MD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Hydroxyeicosatetraenoic Acids
Kidney Diseases
Kidney Medulla
Kidney Tubules
Protective Agents
Rats
Rats, Sprague-Dawley
Regional Blood Flow
Reperfusion Injury
Sodium