期刊
KIDNEY INTERNATIONAL
卷 75, 期 5, 页码 511-517出版社
ELSEVIER SCIENCE INC
DOI: 10.1038/ki.2008.600
关键词
20-HETE; acute kidney injury; acute renal failure; HET0016; ischemia-reperfusion
资金
- NHLBI NIH HHS [P01 HL029587-259002, P01 HL029587-250003, P01 HL029587, HL29546, R01 HL036279, HL36279, R37 HL036279-22, R37 HL036279] Funding Source: Medline
- NIDDK NIH HHS [P01 DK038226, DK38226] Funding Source: Medline
- NIGMS NIH HHS [R01 GM031278, GM31278] Funding Source: Medline
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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