PMID- 10720951
OWN - NLM
STAT- MEDLINE
DCOM- 20000518
LR  - 20131121
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 57
IP  - 3
DP  - 2000 Mar
TI  - Effect of angiotensin-converting enzyme inhibition on growth factor mRNA in 
      chronic renal allograft rejection in the rat.
PG  - 982-91
AB  - BACKGROUND: Despite considerable progress in immunosuppression, the incidence of 
      chronic renal allograft rejection has not decreased. Recent studies have revealed 
      that angiotensin-converting enzyme (ACE) inhibition ameliorates graft 
      arteriosclerosis, glomerulosclerosis, and tubular atrophy. Moreover, it decreases 
      systemic and glomerular capillary hydrostatic pressure in a rat kidney allograft 
      model. We evaluated the effects of the ACE inhibitor enalapril on cytokine and 
      growth factor expression in chronically rejecting rat kidney allografts. METHODS: 
      Kidneys of Fisher (F344) rats were orthotopically transplanted into Lewis (Lew) 
      rats. To prevent acute rejection, cyclosporine A (1.5 mg/kg/day) was given to all 
      recipients during the first 10 days after transplantation. Enalapril (60 mg/L) or 
      vehicle was added to the drinking water 10 days after transplantation. Animals 
      were harvested 20 weeks after transplantation for histologic and immunohistologic 
      studies, as well as for evaluation of cytokine and growth factor mRNA by 
      semiquantitative polymerase chain reaction. RESULTS: Controls developed severe 
      signs of chronic rejection, such as glomerular and vascular lesions, associated 
      with a large number of infiltrating leukocytes. Enalapril-treated animals 
      developed less proteinuria and other signs of chronic rejection. The mRNA levels 
      of transforming growth factor-beta 1 (TGF-beta 1), platelet-derived growth factor 
      A and B chain (PDGF A and B), insulin-like growth factor-I (IGF-I), interleukin-1 
      (IL-1), and monocyte chemoattractant protein-1 (MCP-1) were significantly reduced 
      in the enalapril group and were most pronounced for IL-1 and PDGF A. In addition, 
      we found an increased level of renal angiotensinogen mRNA after treatment with 
      enalapril. CONCLUSIONS: Treatment with enalapril attenuated the development of 
      proteinuria, ameliorated morphological damage, decreased leukocyte infiltration, 
      and prevented a rise in renal mRNA levels of growth factors and cytokines in 
      kidney grafts in a rat model of chronic renal allograft rejection.
FAU - Szabo, A
AU  - Szabo A
AD  - Department of Nephrology, University Hospital Essen, Germany.
FAU - Lutz, J
AU  - Lutz J
FAU - Schleimer, K
AU  - Schleimer K
FAU - Antus, B
AU  - Antus B
FAU - Hamar, P
AU  - Hamar P
FAU - Philipp, T
AU  - Philipp T
FAU - Heemann, U
AU  - Heemann U
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Growth Substances)
RN  - 0 (RNA, Messenger)
RN  - 69PN84IO1A (Enalapril)
SB  - IM
CIN - Am J Kidney Dis. 2001 Apr;37(4):866-70. PMID: 11273890
MH  - Angiotensin-Converting Enzyme Inhibitors/*pharmacology
MH  - Animals
MH  - Chronic Disease
MH  - Diuresis/drug effects
MH  - Enalapril/*pharmacology
MH  - Graft Rejection/*metabolism/pathology
MH  - Growth Substances/*genetics
MH  - Kidney/metabolism/pathology
MH  - *Kidney Transplantation
MH  - Male
MH  - Proteinuria/urine
MH  - RNA, Messenger/*metabolism
MH  - Rats
MH  - Rats, Inbred F344
MH  - Rats, Inbred Lew
EDAT- 2000/03/18 09:00
MHDA- 2000/05/20 09:00
CRDT- 2000/03/18 09:00
PHST- 2000/03/18 09:00 [pubmed]
PHST- 2000/05/20 09:00 [medline]
PHST- 2000/03/18 09:00 [entrez]
AID - S0085-2538(15)46830-9 [pii]
AID - 10.1046/j.1523-1755.2000.00926.x [doi]
PST - ppublish
SO  - Kidney Int. 2000 Mar;57(3):982-91. doi: 10.1046/j.1523-1755.2000.00926.x.