Effects of Pre- and Post-ischemic Treatments with FK409, a Nitric Oxide Donor, on Ischemia/Reperfusion-Induced Renal Injury and Endothelin-1 Production in Rats(Pharmacology)

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We have demonstrated that ischemic acute renal failure (ARF) is attenuated by pre-ischemic treatment with a spontaneous nitric oxide (NO) donor, (±)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409). In the present study, we evaluated the effect of post-ischemic treatment with FK409 on ARF, compared with the pre-ischemic treatment effect. Ischemic ARF was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. At 24h after reperfusion, renal function in untreated ARF rats markedly decreased. In addition, increases in renal contents of endothelin-1 (ET-1), a deleterious mediator in the pathogenesis of ischemic ARF, were evident in untreated ARF rats at 24h after reperfusion. Pre-ischemic treatment with FK409 (1 or 3mg/kg, i.v.) at 5 min before ischemia attenuated ischemia/reperfusion-induced renal dysfunction and increased ET-1 contents after reperfusion. In contrast, post-ischemic treatment with FK409 (3 or 10 mg/kg, i.v.) at 6h after reperfusion aggravated the renal injury, but did not affect the increased ET-1 content after reperfusion. These results suggest that pre-ischemic treatment with FK409 exerts renoprotective effects on ischemic ARF, probably through the suppression of renal ET-1 overproduction, whereas post-ischemic treatment with the NO donor worsens the ischemia/reperfusion-induced renal injury, through mechanisms unrelated to the ET-1 production after reperfusion.
公益社団法人日本薬学会の論文
2006-03-01

Effects of Pre- and Post-ischemic Treatments with FK409, a Nitric Oxide Donor, on Ischemia/Reperfusion-Induced Renal Injury and Endothelin-1 Production in Rats(Pharmacology)

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