title: Glomerular and tubular function during AT1 receptor blockade in pigs with neonatal induced partial ureteropelvic obstruction.
abstract: 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.
authors.affiliation: Department of Clinical Physiology and Nuclear Medicine, University of Aarhus, Denmark.
authors.forename: Anni
authors.initials: A
authors.lastname: Eskild-Jensen
authors.forename: Klaus
authors.initials: K
authors.lastname: Thomsen
authors.forename: Christine
authors.initials: C
authors.lastname: Rungø
authors.forename: Luis S
authors.initials: LS
authors.lastname: Ferreira
authors.forename: Lene Fogt
authors.initials: LF
authors.lastname: Paulsen
authors.forename: Yazan F
authors.initials: YF
authors.lastname: Rawashdeh
authors.forename: Jens Randel
authors.initials: JR
authors.lastname: Nyengaard
authors.forename: Søren
authors.initials: S
authors.lastname: Nielsen
authors.forename: Jens Christian
authors.initials: JC
authors.lastname: Djurhuus
authors.forename: Jørgen
authors.initials: J
authors.lastname: Frøkiaer
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D051399:Aquaporin 2 / Q000378:metabolism; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000254:growth & development / Q000503:physiopathology*; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D006180:Proton-Translocating ATPases / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D034421:Sus scrofa; D013777:Tetrazoles / Q000494:pharmacology; D014517:Ureteral Obstruction / Q000378:metabolism / Q000503:physiopathology*; D014867:Water / Q000378:metabolism
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D051399:Aquaporin 2; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; D013777:Tetrazoles; D014867:Water; D012964:Sodium; D019001:Nitric Oxide Synthase; D006180:Proton-Translocating ATPases; C081643:candesartan; D019331:NG-Nitroarginine Methyl Ester