PMID- 14605275
OWN - NLM
STAT- MEDLINE
DCOM- 20040427
LR  - 20190513
IS  - 0931-0509 (Print)
IS  - 0931-0509 (Linking)
VI  - 18
IP  - 12
DP  - 2003 Dec
TI  - Perturbed medullary tubulogenesis in neonatal rat exposed to renin-angiotensin 
      system inhibition.
PG  - 2534-41
AB  - BACKGROUND: Pharmacological interruption of the angiotensin II type-1 receptor 
      (AT(1)) signalling during nephrogenesis in rats induces irreversible 
      abnormalities in kidney morphology, comprising papillary atrophy and 
      tubulointerstitial damage, which are characterized by tubular dilatation/atrophy 
      and interstitial inflammation/fibrosis. This study determined the time course for 
      development of tubular structural and inflammatory changes and possible cytokine 
      production in the renal medulla of newborn rats exposed to angiotensin-converting 
      enzyme (ACE) inhibition. Additionally, medullary expression of E-cadherin, a 
      marker for tubular formation, was investigated in ACE-inhibited rats. METHODS: 
      Newborn rats were exposed (postnatal days 0-12) to ACE inhibitor enalapril and 
      killed at days 1, 2, 4, 9 and 13. One kidney was used for morphological 
      evaluation and the other for immunohistochemistry, using antibodies directed 
      against monocytes/macrophages, T cells and E-cadherin on frozen sections. In a 
      separate experiment, rats were treated for 9 days and had their kidneys processed 
      for western immunoblot and immunohistochemistry, where antibodies directed 
      against monocyte chemoattractant protein-1 (MCP-1) and tumour necrosis 
      factor-alpha (TNF-alpha) were used on paraffin sections. RESULTS: In renal 
      medulla from enalapril-treated rats, volume fractions of tubular lumens and 
      interstitium were increased from postnatal days 2 and 4, respectively, while that 
      of tubular cells was decreased from 4 days of age. Concomitant loss and/or 
      reduction in E-cadherin expression (from day 2) was observed in dilated medullary 
      tubules of enalapril-treated rats. Furthermore, in the medulla of 
      enalapril-treated rats, the increased number of ED2+ (resident macrophages) 
      cells, followed by the increase in ED1+ (monocytes/macrophages) and CD4+ T cells, 
      was observed at days 9 and 13, respectively. This was accompanied by increased 
      medullary expression of TNF-alpha at day 9. CONCLUSIONS: Neonatal ACE inhibition 
      perturbs medullary tubulogenesis, as indicated by tubular dilatation and a lack 
      of E-cadherin expression in these tubules. Macrophage/monocyte-mediated immune 
      response is a secondary event, coincidentally associated with the up-regulation 
      of TNF-alpha.
FAU - Lasaitiene, Daina
AU  - Lasaitiene D
AD  - Department of Physiology, Institute of Physiology and Pharmacology, University of 
      Gothenburg, Box 432, S-405 30 Gothenburg, Sweden. 
      daina.lasaitiene@fysiologi.gu.se
FAU - Chen, Yun
AU  - Chen Y
FAU - Guron, Gregor
AU  - Guron G
FAU - Marcussen, Niels
AU  - Marcussen N
FAU - Tarkowski, Andrzej
AU  - Tarkowski A
FAU - Telemo, Esbjorn
AU  - Telemo E
FAU - Friberg, Peter
AU  - Friberg P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nephrol Dial Transplant
JT  - Nephrology, dialysis, transplantation : official publication of the European 
      Dialysis and Transplant Association - European Renal Association
JID - 8706402
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Cadherins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 69PN84IO1A (Enalapril)
SB  - IM
MH  - Angiotensin-Converting Enzyme Inhibitors/*adverse effects
MH  - Animals
MH  - Animals, Newborn
MH  - Cadherins/biosynthesis
MH  - Enalapril/*adverse effects
MH  - Female
MH  - Kidney Medulla/abnormalities/*embryology/metabolism
MH  - Kidney Tubules/abnormalities/*embryology/metabolism
MH  - Models, Animal
MH  - Rats
MH  - Rats, Wistar
MH  - Renin-Angiotensin System/*drug effects/physiology
MH  - Time Factors
MH  - Tumor Necrosis Factor-alpha/biosynthesis
MH  - Urogenital Abnormalities/chemically induced/*embryology/metabolism
EDAT- 2003/11/08 05:00
MHDA- 2004/04/28 05:00
CRDT- 2003/11/08 05:00
PHST- 2003/11/08 05:00 [pubmed]
PHST- 2004/04/28 05:00 [medline]
PHST- 2003/11/08 05:00 [entrez]
AID - 10.1093/ndt/gfg447 [doi]
PST - ppublish
SO  - Nephrol Dial Transplant. 2003 Dec;18(12):2534-41. doi: 10.1093/ndt/gfg447.