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

54 Citations (Scopus)

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 2009

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Reperfusion Injury
Kidney
Wounds and Injuries
Sodium
Heart Injuries
Laser-Doppler Flowmetry
Glomerular Filtration Rate
Acute Kidney Injury
Arachidonic Acid
Brain Injuries
Reperfusion
Sprague Dawley Rats
Arterial Pressure
N-(20-hydroxyeicosa-5,14-dienoyl)glycine
20-hydroxy-5,8,11,14-eicosatetraenoic acid
Urine
20-hydroxyeicosa-6(Z),15(Z)-dienoic acid

Keywords

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

ASJC Scopus subject areas

  • Nephrology

Cite this

Regner, K. R., Zuk, A., Van Why, S. K., Shames, B. D., Ryan, R. P., Falck, J. 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

Protective effect of 20-HETE analogues in experimental renal ischemia reperfusion injury. / Regner, Kevin R.; Zuk, Anna; Van Why, Scott K.; Shames, Brian D.; Ryan, Robert P.; Falck, J R; Manthati, Vijay L.; McMullen, Meghan E.; Ledbetter, Steven R.; Roman, Richard J.

In: Kidney International, Vol. 75, No. 5, 03.2009, p. 511-517.

Research output: Contribution to journalArticle

Regner, KR, Zuk, A, Van Why, SK, Shames, BD, Ryan, RP, Falck, JR, Manthati, VL, McMullen, ME, Ledbetter, SR & Roman, RJ 2009, 'Protective effect of 20-HETE analogues in experimental renal ischemia reperfusion injury', Kidney International, vol. 75, no. 5, pp. 511-517. https://doi.org/10.1038/ki.2008.600
Regner, Kevin R. ; Zuk, Anna ; Van Why, Scott K. ; Shames, Brian D. ; Ryan, Robert P. ; Falck, J R ; Manthati, Vijay L. ; McMullen, Meghan E. ; Ledbetter, Steven R. ; Roman, Richard J. / Protective effect of 20-HETE analogues in experimental renal ischemia reperfusion injury. In: Kidney International. 2009 ; Vol. 75, No. 5. pp. 511-517.
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