2002 Global Researcher Conference Proceeding
April 26 - 28, 2002
| Conference: | 2002 Global Researcher Conference |
|---|---|
| Title: | Downregulation of renal aquaporins and sodium transporters in rats with bilateral ureteral obstruction (BUO) is prevented by a-MSH treatment |
| Authors: | Li, Chunling; Wang, Weidong; Kwon, Tae-Hwan; Knepper, Mark; Nielsen, Soren; Frokiaer, Jorgen; Sardeli, C. |
| Institutions: | University of Aarhus, National Institutes of Health, The Water and Salt Research Center, University of Aarhus |
Urinary tract obstruction is a common manifestation which may be caused by congenital malformations of the kidney and urinary tract or acquired later in life. Urinary tract obstruction may cause obstructive nephropathy which is characterized by unique reduction in renal function including development of nephrogenic diabetes insipidus (NDI). Obstructive nephropathy is a complex disease and inflammation is an important pathophysiological factor in this disease. The aims of these studies were to study the effect of a 24 h bilateral ureteral obstruction (BUO), and release of BUO (BUO-R) for 5 and 48 h on renal aquaporins (AQPs), sodium transporters and urine output (UO). Consistent with previous observations BUO was associated with a marked downregulation of AQP1, AQP2 and AQP3. Release of BUO was associated with a dramatic polyuria and reduced urine osmolality (559±38 vs. 2262±232 mOsmol/kgH2O in controls, p<0.05). Consistent with this AQP1, 2 and 3 were persistently downregulated (AQP1: 24±5% vs.100±10% in controls; AQP2: 13±5 vs 100±1%; AQP3: 10±5% vs.100±1%). BUO is associated with an inflammatory response and we therefore examined whether treatment with the anti-inflammatory drug a-MSH could prevent downregulation of renal aquaporins. Administration of a-MSH from onset of obstruction significantly prevented dysregulation of AQP2 (38±5% with a-MSH treatment, n=10, vs. 13±4% without a-MSH treatment,n=10, p<0.05) and AQP3 (44±3% vs. 19±4%, p<0.05) during obstruction whereas AQP1 and AQP3 downregulation was partially prevented at 5h and 48h after BUO-R. Semiquantitative immunoblotting showed that in response to BUO-R for 5 h a-MSH treatment significantly increased AQP1 expression (81±21% vs.7±2%, p<0.05) and AQP3 expression (34±4% vs. 14±5%, p<0.05). After BUO-R for 48 hours AQP1 expression in whole kidney was increased from 24±5% (n=5) to 58±6% (n=6, p<0.05). UO did not respond to a-MSH treatment. However, a-MSH markedly prevented the increase in p-osmolality (311±2 vs. 327±7mOsm/kgH2O,p<0.05), p-creatinine (79±34 vs.160±34 mmol/l, p<0.05) and p-urea (13±2 vs. 35±9 mmol/l, p<0.05). In conclusion, BUO and BUO-R is associated with a marked dysregulation of AQP1, AQP2 and AQP3 which is prevented by a-MSH treatment suggesting that a-MSH can protect kidney function in conditions with urinary tract obstruction.
The ureter is a fibromuscular tube which conveys urine from the kidney to the bladder. Each kidney has a ureter attached to it, thus most mammals have two. When the ureters are blocked, it is called a urinary tract obstruction. This condition reduces the kidneys' ability to function and often results in inflammation of the renal tissue. Frokiaer, et al., studied the effect on rats when they had both ureters blocked (BUO) for 24 hours, and what the effect was 5 and 48 hours after the blockade was released (BUO-R). They were specifically looking for the effect of these conditions on kidney aquaporins (AQPs), sodium transporters, and urine output (UO). The researchers found that BUO was associated with significantly lower numbers of AQPs 1, 2 and 3, and BUO-R was associated with UO. Also, the urine was far more dilute than normal.
Since BUO is associated with inflammation, the researchers tested whether an anti-inflammatory drug, a-MSH would prevent the lower numbers of AQPs associated with BUO. They found AQP2 and AQP3 were produced in significantly higher, but still below normal, numbers by BUO rats treated with a-MSH. This drug also helped to prevent the fall in numbers of AQP1 and AQP3 after BUO-R.
a-MSH did not affect UO, though it did help prevent the increase in plasma concentration overall and the concentrations of creatinine and urea in particular. These findings suggest a-MSH can protect kidney function when the urinary tract is obstructed.