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This Article Full Text Full Text (PDF) All Versions of this Article: 292/3/F921    most recent 00407.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Eskild-Jensen, A. Articles by Frøkiær, J. Search for Related Content PubMed PubMed Citation Articles by Eskild-Jensen, A. Articles by Frøkiær, J.

Glomerular and tubular function during AT1 receptor blockade in pigs with neonatal induced partial ureteropelvic obstruction

¹Department of Clinical Physiology and Nuclear Medicine, and ²Institute of Clinical Medicine, University of Aarhus, and ³Department of Urology, Aarhus University Hospital, Aarhus; ⁴Centre for Basic Psychiatric Research, Aarhus University Hospital; ⁵Stereology and Electron Microscopy Research Laboratory and MIND Center and ⁶The Water and Salt Research Center, University of Aarhus, Aarhus, Denmark

Submitted 16 October 2006 ; accepted in final form 21 November 2006

Previously, we showed that neonatal induced chronic partial unilateral ureteral obstruction (PUUO) of the multipapillary pig kidney decreased glomerular filtration rate (GFR) of the obstructed kidney. We hypothesized that ANG II and nitric oxide (NO) are important for the changes in renal function and in the present study we examined the effects of chronic AT1 receptor blockade using CV-11974 (0.12 mg/h candesartan from age 23 to 30 days) on kidney function development after PUUO was induced in 2-day-old piglets. Moreover, the effect of superimposed acute NO inhibition using N^G-nitro-L-arginine methyl ester (L-NAME; 15 mg/kg) was examined to identify if this has diagnostic potential. PUUO significantly increased GFR in the nonobstructed contralateral kidney independent of candesartan. In candesartan-treated piglets, the L-NAME-induced GFR reduction seen in normal and nonobstructed kidneys was absent in the partial obstructed kidneys. Urine output and fractional excretion of water were increased from the partial obstructed kidneys. Consistent with this immunohistochemical analyses showed a reduced aquaporin-2 labeling in the collecting duct principal cells. Moreover, renal sodium handling was compromised by PUUO evidenced by an increased fractional excretion of sodium which was enhanced by candesartan treatment. In conclusion, our findings suggest that the counterbalance between AT1 receptor-mediated vasoconstriction and NO-mediated vasodilatation which maintain GFR in normal young porcine kidneys is changed by neonatal induced chronic PUUO. This may have diagnostic potential in children with suspected congenital obstruction. Our results also demonstrate compromised tubular functions in response to chronic PUUO despite preservation of glomerular function.

hydronephrosis; stereology; glomerular filtration rate; aquaporin 2

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				A. Eskild-Jensen, L. F. Paulsen, L. Wogensen, P. Olesen, L. Pedersen, J. Frokiaer, and J. R. Nyengaard AT1 receptor blockade prevents interstitial and glomerular apoptosis but not fibrosis in pigs with neonatal induced partial unilateral ureteral obstruction Am J Physiol Renal Physiol, June 1, 2007; 292(6): F1771 - F1781. [Abstract] [Full Text] [PDF]