PMID- 10844632
OWN - NLM
STAT- MEDLINE
DCOM- 20000824
LR  - 20131121
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 57
IP  - 6
DP  - 2000 Jun
TI  - Renal allograft protection with losartan in Fisher-->Lewis rats: hemodynamics, 
      macrophages, and cytokines.
PG  - 2618-25
AB  - BACKGROUND: We sought to assess the effects of angiotensin receptor blockade on 
      glomerular hypertension, macrophage recruitment, and cytokine expression, all of 
      which contribute to the development of chronic graft injury in this model. 
      METHODS: The effects of treatment with the specific angiotensin II type 1 (AT1) 
      receptor antagonist, losartan, were assessed over 24 weeks in F344-->LEW rats 
      (LOS, N = 9) versus vehicle-treated F344-->LEW controls (CON, N = 9). RESULTS: 
      UprotV rose progressively in CON (from 7.0 +/- 2.9 to 41 +/- 17 mg/day at 24 wk) 
      but remained at baseline in LOS (4.2 +/- 0.6 to 9.4 +/- 1.3 mg/day, P < 0.05 vs. 
      CON). Glomerular capillary pressure (PGC) was increased in CON (71 +/- 1 mm Hg at 
      week 20), but remained within the normal range in LOS rats (54 +/- 2 mm Hg, P < 
      0.05). Glomerulosclerosis averaged 0.3 +/- 0.2% in LOS versus 4 +/- 2% in CON 
      rats (P < 0.05). Tubulointerstitial injury was minimal in both LOS and CON rats 
      (+). The overexpression of renal cortical cytokine mRNA levels for the monocyte 
      chemoattractants, monocyte chemoattractant protein-1 (MCP-1) and RANTES, as well 
      as interleukin-1, inducible nitric oxide synthase, and transforming growth 
      factor-beta, assessed by competitive reverse transcription-polymerase chain 
      reaction, was suppressed in LOS versus CON rats at 20 weeks. Macrophage and 
      T-cell numbers were decreased, and MCP-1, RANTES, and intercellular adhesion 
      molecule-1 staining in the graft, identified by immunohistochemistry, were 
      attenuated in LOS versus CON rats. CONCLUSIONS: The renoprotective effects of 
      losartan in F344-->LEW rats were associated with lowered PGC, inhibition of 
      macrophage chemoattractants and recruitment, and suppression of 
      macrophage-associated cytokines at 20 weeks. These findings suggest that chronic 
      allograft injury in F344-->LEW rats is, to a large extent, mediated by 
      angiotensin II-dependent mechanisms and that these involve glomerular 
      hemodynamics, macrophages, and macrophage-associated cytokines.
FAU - Ziai, F
AU  - Ziai F
AD  - Renal Division, Department of Medicine and Department of Pathology, Surgical 
      Research Laboratories, Harvard Medical School and Brigham and Women's Hospital, 
      Boston, Massachusetts 02115, USA.
FAU - Nagano, H
AU  - Nagano H
FAU - Kusaka, M
AU  - Kusaka M
FAU - Coito, A J
AU  - Coito AJ
FAU - Troy, J L
AU  - Troy JL
FAU - Nadeau, K C
AU  - Nadeau KC
FAU - Rennke, H G
AU  - Rennke HG
FAU - Tilney, N L
AU  - Tilney NL
FAU - Brenner, B M
AU  - Brenner BM
FAU - MacKenzie, H S
AU  - MacKenzie HS
LA  - eng
GR  - 9PO1DK46190-23/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Angiotensin Receptor Antagonists)
RN  - 0 (Cytokines)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 0 (Receptor, Angiotensin, Type 2)
RN  - JMS50MPO89 (Losartan)
SB  - IM
MH  - Angiotensin Receptor Antagonists
MH  - Animals
MH  - Cytokines/metabolism
MH  - Graft Rejection/metabolism
MH  - Hemodynamics
MH  - Kidney/metabolism/pathology/physiopathology
MH  - Kidney Glomerulus/blood supply
MH  - *Kidney Transplantation
MH  - Losartan/*therapeutic use
MH  - Male
MH  - Rats
MH  - Rats, Inbred F344
MH  - Rats, Inbred Lew
MH  - Receptor, Angiotensin, Type 1
MH  - Receptor, Angiotensin, Type 2
MH  - Transplantation, Homologous
EDAT- 2000/06/09 09:00
MHDA- 2000/08/29 11:01
CRDT- 2000/06/09 09:00
PHST- 2000/06/09 09:00 [pubmed]
PHST- 2000/08/29 11:01 [medline]
PHST- 2000/06/09 09:00 [entrez]
AID - S0085-2538(15)47022-X [pii]
AID - 10.1046/j.1523-1755.2000.00122.x [doi]
PST - ppublish
SO  - Kidney Int. 2000 Jun;57(6):2618-25. doi: 10.1046/j.1523-1755.2000.00122.x.