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1 The Water and Salt Research Center, University of Aarhus, Aarhus, Denmark; Institute of Clinical Medicine, University of Aarhus, Aarhus, Denmark
2 The MR Research Center, University of Aarhus, Aarhus, Denmark
3 Lab. of Kidney and Electrolyte Metabolism, NHLBI, NIH, Bethesda, Maryland, United States
4 Institute of Clinical Medicine, University of Aarhus, Aarhus, Denmark
5 The Water and Salt Research Center, University of Aarhus, Aarhus, Denmark; Institute of Anatomy, University of Aarhus, Aarhus, Denmark
6 Department of Urology, University of Arhus, Aarhus, Denmark
7 The Water and Salt Research Center, University of Aarhus, Skejby Hospital, Denmark; Institute of Clinical Medicine, University of Aarhus, Aarhus, Denmark
* To whom correspondence should be addressed. E-mail: jf{at}ki.au.dk.
Angiotensin II (ANG II) plays an important role for the development of obstructive nephropathy. Here we examined the effects of the ANG II receptor type 1 (AT1R) blockade using candesartan (CAN) on long-term renal molecular and functional changes in response to partial unilateral ureteral obstruction (PUUO). Newborn rats were subjected to severe PUUO or sham operation (SHAM) within the first 48 hr of life. CAN was provided in the drinking water (10 mg/kg/day) from day 21 of life until 10 weeks of age. Renal blood flow (RBF) was evaluated by MRI, glomerular filtration rate (GFR) was measured using the renal clearance of 51Cr-EDTA, and the renal expression of Na,K-ATPase and the collecting duct water channel AQP2 were examined by immunoblotting and immunocytochemistry. At ten weeks of age, PUUO significantly reduced RBF and GFR compared to sham. CAN prevented the RBF reduction and attenuated the GFR reduction. PUUO was also associated with a significant downregulation in the expression of Na,K-ATPase and AQP2, which were also prevented by CAN. These findings were confirmed by immunocytochemistry. Consistent with this, CAN treatment partly prevented the reduction in solute free water reabsorption and attenuated fractional sodium excretion in rats with PUUO. In conclusion, CAN prevents or attenuates the reduction in RBF, GFR and dysregulation of AQP2 and Na,K-ATPase in response to congenital PUUO in rats, suggesting that AT1R blockade may protect the neonatally obstructed kidney against development of obstructive nephropathy.
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