Abstract | BACKGROUND: METHODS: I/R-induced ARF was established in rats by 40-minute temporary bilateral obstruction of renal arteries, and rats were kept in metabolic cages for urine measurements. After 2 or 4 days following EPO and/or alpha-MSH treatment, kidneys were removed to determine the expression levels of AQPs and sodium transporters by semiquantitative immunoblotting. RESULTS: Rats with ARF showed significant renal insufficiency, increased urine output, and high fractional excretion of urinary sodium. Consistent with this, immunoblotting and immunocytochemistry revealed that the kidney expression of AQPs (AQP-1, -2 and -3) and sodium transporters [Na,K- ATPase, rat type 1 bumetanide-sensitive Na-K-2Cl cotransporter (BSC-1), Na/H exchanger type 3 (NHE3), and thiazide-sensitive sodium chloride cotransporter ( TSC)] in ARF rats was significantly decreased compared to sham-operated control rats. In contrast, EPO treatment at the time of ischemia of rats with ARF significantly prevented the ischemia-induced down-regulation of renal AQPs and sodium transporters and in parallel improved the urinary concentrating capability and renal sodium reabsorption. Importantly, similar effects were observed following the initiation of EPO or alpha-MSH treatment 4 hours after the onset of ischemia injury. Moreover, the combination of EPO with alpha-MSH potentiated the beneficial effects of single compound treatment. CONCLUSION: EPO and/or alpha-MSH treatment significantly prevent I/R-induced injuries such as urinary-concentrating defects and down-regulation of renal AQPs and sodium transporters.
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Authors | Hong Gong, Weidong Wang, Tae-Hwan Kwon, Thomas Jonassen, Chunling Li, Troels Ring, Jørgen FrøkiAEr, Søren Nielsen |
Journal | Kidney international
(Kidney Int)
Vol. 66
Issue 2
Pg. 683-95
(Aug 2004)
ISSN: 0085-2538 [Print] United States |
PMID | 15253723
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Aqp1 protein, rat
- Aqp2 protein, rat
- Aqp3 protein, rat
- Aquaporin 2
- Aquaporins
- Slc9a3 protein, rat
- Sodium-Hydrogen Exchanger 3
- Sodium-Hydrogen Exchangers
- Water
- Erythropoietin
- Aquaporin 1
- Aquaporin 3
- alpha-MSH
- Sodium
- Sodium-Potassium-Exchanging ATPase
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Topics |
- Acute Kidney Injury
(drug therapy, metabolism)
- Animals
- Antibody Specificity
- Aquaporin 1
- Aquaporin 2
- Aquaporin 3
- Aquaporins
(immunology, metabolism)
- Down-Regulation
(drug effects)
- Erythropoietin
(pharmacology)
- Immunoblotting
- Kidney
(drug effects, metabolism)
- Male
- Rats
- Rats, Wistar
- Reperfusion Injury
(drug therapy, metabolism)
- Sodium
(metabolism)
- Sodium-Hydrogen Exchanger 3
- Sodium-Hydrogen Exchangers
(metabolism)
- Sodium-Potassium-Exchanging ATPase
(metabolism)
- Water
(metabolism)
- alpha-MSH
(pharmacology)
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