TY - JOUR
T1 - EPO and α-MSH prevent ischemia/reperfusion-induced down-regulation of AQPs and sodium transporters in rat kidney
AU - Gong, Hong
AU - Wang, Weidong
AU - Kwon, Tae Hwan
AU - Jonassen, Thomas
AU - Li, Chunling
AU - Ring, Troels
AU - Frøkiær, Jørgen
AU - Nielsen, Søren
PY - 2004/8
Y1 - 2004/8
N2 - Background. Ischemia-induced acute renal failure (ARF) is known to be associated with significant impairment of urinary concentrating ability and down-regulation of renal aquaporins (AQPs) and sodium transporters in rats. We tested whether treatment with erythropoietin (EPO) or α-melanocyte- stimulating hormone (α-MSH) in combination with EPO reduces the renal ischemia/reperfusion (I/R) injury and prevents the down-regulation of renal AQPs and major sodium transporters. 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 α-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 α-MSH treatment 4 hours after the onset of ischemia injury. Moreover, the combination of EPO with α-MSH potentiated the beneficial effects of single compound treatment. Conclusion. EPO and/or α-MSH treatment significantly prevent I/R-induced injuries such as urinary-concentrating defects and down-regulation of renal AQPs and sodium transporters.
AB - Background. Ischemia-induced acute renal failure (ARF) is known to be associated with significant impairment of urinary concentrating ability and down-regulation of renal aquaporins (AQPs) and sodium transporters in rats. We tested whether treatment with erythropoietin (EPO) or α-melanocyte- stimulating hormone (α-MSH) in combination with EPO reduces the renal ischemia/reperfusion (I/R) injury and prevents the down-regulation of renal AQPs and major sodium transporters. 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 α-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 α-MSH treatment 4 hours after the onset of ischemia injury. Moreover, the combination of EPO with α-MSH potentiated the beneficial effects of single compound treatment. Conclusion. EPO and/or α-MSH treatment significantly prevent I/R-induced injuries such as urinary-concentrating defects and down-regulation of renal AQPs and sodium transporters.
KW - Acute renal failure
KW - Aquaporin
KW - Erythropoietin
KW - Sodium transporter
KW - Urinary concentration
KW - α-melanocyte stimulating hormone
UR - http://www.scopus.com/inward/record.url?scp=3242772957&partnerID=8YFLogxK
U2 - 10.1111/j.1523-1755.2004.00791.x
DO - 10.1111/j.1523-1755.2004.00791.x
M3 - Article
C2 - 15253723
AN - SCOPUS:3242772957
SN - 0085-2538
VL - 66
SP - 683
EP - 695
JO - Kidney International
JF - Kidney International
IS - 2
ER -