α-MSH prevents impairment in renal function and dysregulation of AQPs and Na-K-ATPase in rats with bilateral ureteral obstruction

被引:19
作者
Li, CL
Shi, YM
Wang, WD
Sardeli, C
Kwon, TH
Thomsen, K
Jonassen, T
Djurhuus, JC
Knepper, MA
Nielsen, S
Frokiær, J
机构
[1] Univ Aarhus, Water & Salt Res Ctr, DK-8230 Aarhus N, Denmark
[2] Univ Aarhus, Inst Anat, DK-8230 Aarhus N, Denmark
[3] Univ Aarhus, Inst Clin Med, DK-8230 Aarhus N, Denmark
[4] Kyungpook Natl Univ, Sch Med, Dept Biochem & Cell Biol, Taegu 702701, South Korea
[5] Inst Basic Psychiat Res, Dept Biol Psychiat, Risskov, Denmark
[6] NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA
[7] Univ Copenhagen, Dept Pharmacol, Copenhagen, Denmark
[8] Univ Aarhus, Hosp Skejby, Dept Clin Physiol & Nucl Med, Water & Salt Res Ctr,Inst Clin Med, DK-8230 Aarhus N, Denmark
关键词
urinary tract obstruction; water channels; sodium pump; urinary concentrating defect;
D O I
10.1152/ajprenal.00282.2004
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
The purpose of this study was to evaluate the effects of the anti-inflammatory hormone alpha-melanocyte-stimulating hormone (alpha-MSH) treatment on renal function and expression of aquaporins (AQPs) and Na-K-ATPase in the kidney in response to 24 h of bilateral ureteral obstruction (BUO) or release of BUO (BUO-R). In rats with 24-h BUO, immunoblotting revealed that downregulation of AQP2 and AQP3 was attenuated (AQP2: 38 +/- 5 vs. 13 +/- 4%; AQP3: 44 +/- 3 vs. 19 +/- 4% of sham levels; P < 0.05), whereas downregulation of Na-K-ATPase was prevented by alpha-MSH treatment (Na-K-ATPase: 94 +/- 7 vs. 35 +/- 5% of sham levels; P < 0.05). Immunocytochemistry confirmed the changes in AQP1 and Na-K-ATPase expression. Renal tubular cell apoptosis was confirmed in BUO kidneys, and alpha-MSH treatment virtually completely abolished apoptosis. Furthermore, we measured glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), respectively. Forty-eight hours after BUO-R demonstrated that alpha-MSH treatment almost completely prevented the decrease in GFR (nontreated: 271 +/- 50; alpha-MSH: 706 +/- 85; sham: 841 +/- 105 mu l(.)min(-1.)100 g body wt(-1), P < 0.05) and ERPF (nontreated: 1,139 +/- 217; alpha-MSH: 2,598 +/- 129; sham: 2,633 +/- 457 mu l(.)min(-1.)100 g body wt(-1), P < 0.05). alpha-MSH treatment also partly prevented the downregulation of AQP1 and Na-K-ATPase expression in rats after BUO-R for 48 h. In conclusion, alpha-MSH treatment significantly prevents impairment in renal function and also prevents downregulation of AQP2, AQP3, and Na-K-ATPase during BUO or AQP1 and Na-K-ATPase after BUO-R, demonstrating a marked renoprotective effect of alpha-MSH treatment in conditions with urinary tract obstruction.
引用
收藏
页码:F384 / F396
页数:13
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