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

Kevin R. Regner, Anna Zuk, Scott K. Van Why, Brian D. Shames, Robert P. Ryan, J R Falck, Vijay L. Manthati, Meghan E. McMullen, Steven R. Ledbetter, Richard J. Roman

Research output: Contribution to journalArticle

58 Scopus 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.

Original languageEnglish (US)
Pages (from-to)511-517
Number of pages7
JournalKidney international
Volume75
Issue number5
DOIs
StatePublished - Mar 1 2009

Keywords

  • 20-HETE
  • Acute kidney injury
  • Acute renal failure
  • HET0016
  • Ischemia-reperfusion

ASJC Scopus subject areas

  • Nephrology

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    Regner, K. R., Zuk, A., Van Why, S. K., Shames, B. D., Ryan, R. P., Falck, J. R., Manthati, V. L., McMullen, M. E., Ledbetter, S. R., & Roman, R. J. (2009). Protective effect of 20-HETE analogues in experimental renal ischemia reperfusion injury. Kidney international, 75(5), 511-517. https://doi.org/10.1038/ki.2008.600