| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 The Water and Salt Research Centre, University of Aarhus, Aarhus, Denmark; Institute of Clinical Medicine, University of Aarhus, Aarhus, Denmark; Institute of Anatomy, University of Aarhus, Aarhus, Denmark; LKEM, NIH, Bethesda, Maryland, United States
* To whom correspondence should be addressed. E-mail: jf{at}ki.au.dk.
The renin angiotensin system is well known to be involved in the pathophysiologic changes in renal function after obstruction of the ureter. Previously, we demonstrated that bilateral ureteral obstruction (BUO) is associated with dramatic changes in the expression of both renal sodium transporters and aquaporin water channels (AQPs). We now examined the effects of the AT1-receptor antagonist, candesartan, on the dysregulation of AQP's and key renal sodium transporters in rats subjected to 24 hours BUO and followed 2 days after release of BUO (BUO-2R). Consistent with previous observations BUO-2R resulted in a significantly decreased expression of AQP1, -2 and -3 compared to control rats. Concomitantly, the rats developed polyuria and a reduced urine osmolality. Moreover, expression of the type 2 Na-phosphate cotransporter (NaPi-2) and type 1 bumetanide sensitive Na-K-2Cl cotransporter (NKCC2) were markedly reduced consistent with postobstructive natriuresis. Candesartan treatment from onset of obstruction attenuated the reduction in GFR (3.1±0.4 vs. 1.7±0.3 ml/min/kg) and partially prevented the reduction in the expression of AQP2 (66 ± 21% vs. 13 ± 2%, n=7; p<0.05), NaPi-2 (84 ± 6% vs. 57 ± 10%, n=7; p<0.05) and NKCC2 (89 ± 12 % vs. 46 % ± 11 n=7; p<0.05). Consistent with this candesartan treatment attenuated the increase in urine output (58 ± 4 vs. 97 ± 5 µl/min/kg, n=7; p<0.01) and the reduction in sodium reabsorption (433 ± 62 vs. 233 ± 45 µmol/min/kg, n=7; p<0.05) normally found in rats subjected to BUO. Moreover, candesartan treatment attenuated induction of cyclooxygenase 2 (COX-2) expression in the inner medulla, suggesting that COX-2 induction in response to obstruction is regulated by angiotensin II. In conclusion, candesartan prevents dysregulation of AQP2, sodium transporters and development of polyuria seen in BUO. This strongly supports the view that candesartan protects kidney function in response to urinary tract obstruction.
This article has been cited by other articles:
|
|
 |
|
  M. H. M. Shimizu, A. Danilovic, L. Andrade, R. A. Volpini, A. B. Liborio, T. R.C. Sanches, and A. C. Seguro N-acetylcysteine protects against renal injury following bilateral ureteral obstruction Nephrol. Dial. Transplant., October 1, 2008; 23(10): 3067 - 3073. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. K. Madala Halagappa, S. Tiwari, S. Riazi, X. Hu, and C. M. Ecelbarger Chronic candesartan alters expression and activity of NKCC2, NCC, and ENaC in the obese Zucker rat Am J Physiol Renal Physiol, May 1, 2008; 294(5): F1222 - F1231. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. B. Sandberg, A. D. M. Riquier, K. Pihakaski-Maunsbach, A. A. McDonough, and A. B. Maunsbach ANG II provokes acute trafficking of distal tubule Na+-Cl cotransporter to apical membrane Am J Physiol Renal Physiol, September 1, 2007; 293(3): F662 - F669. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Coleman, J. J. Minor, L. E. Burt, B. A. Thornhill, M. S. Forbes, and R. L. Chevalier Angiotensin AT1-receptor inhibition exacerbates renal injury resulting from partial unilateral ureteral obstruction in the neonatal rat Am J Physiol Renal Physiol, July 1, 2007; 293(1): F262 - F268. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. O. Topcu, M. Pedersen, R. Norregaard, G. Wang, M. Knepper, J. C. Djurhuus, S. Nielsen, T. M. Jorgensen, and J. Frokiaer Candesartan prevents long-term impairment of renal function in response to neonatal partial unilateral ureteral obstruction Am J Physiol Renal Physiol, February 1, 2007; 292(2): F736 - F748. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
