alpha-MSH prevents impairment in renal function and dysregulation of AQPs and Na-K-ATPase in rats with bilateral ureteral obstruction.
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 microl x 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 microl x 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.
Li
Chunling
C
The Water and Salt Research Center, Institute of Clinical Medicine, University of Aarhus, Brendstrupgaardsvej, DK-8230 Aarhus N, Denmark.
Shi
Yimin
Y
Wang
Weidong
W
Sardeli
Chrysanthi
C
Kwon
Tae-Hwan
TH
Thomsen
Klaus
K
Jonassen
Thomas
T
Djurhuus
Jens Christian
JC
Knepper
Mark A
MA
Nielsen
Søren
S
Frøkiaer
Jørgen
J
D000818:Animals; D020346:Aquaporins / Q000378:metabolism*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006728:Hormones / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism / Q000648:ultrastructure; D007672:Kidney Cortex / Q000378:metabolism*; D007684:Kidney Tubules / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D009929:Organ Size; D051381:Rats; D011913:Rats, Inbred BB; D017595:Renal Plasma Flow / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D014517:Ureteral Obstruction / Q000378:metabolism / Q000503:physiopathology*; D000521:alpha-MSH / Q000494:pharmacology*
D020346:Aquaporins; D006728:Hormones; D000521:alpha-MSH; D000254:Sodium-Potassium-Exchanging ATPase