PMID- 16113589
OWN - NLM
STAT- MEDLINE
DCOM- 20060524
LR  - 20170118
IS  - 1660-2137 (Electronic)
IS  - 1660-2137 (Linking)
VI  - 101
IP  - 4
DP  - 2005
TI  - Statin monotherapy attenuates renal injury in a salt-sensitive hypertension model 
      of renal disease.
PG  - p82-91
AB  - BACKGROUND: Several salutary biological effects of statins have been described. 
      We sought to investigate more closely the anti-inflammatory and antiproliferative 
      effects of simvastatin (SIMV) in a model of hypertension and progressive renal 
      disease, as well as its effects on the cyclin-cdk inhibitors p21 and p27. 
      METHODS: Munich-Wistar rats received the nitric oxide (NO) synthase inhibitor 
      L-NAME (25 mg/kg/day p.o.) for 20 days accompanied by a high-salt diet (HS, 3% 
      Na) and then were kept on HS for 60 days. Animals were then divided into two 
      groups: vehicle (VH) or SIMV 2 mg/kg/day p.o. Albuminuria and tail-cuff pressure 
      were determined at 30 and 60 days. RT-PCR was done to assess renal expression of 
      TGF-beta1, collagen I and III, fibronectin, p27, p21 and monocyte chemoattractant 
      protein-1 (MCP-1). Renal protein expression was assessed by Western blot 
      (proliferating cell nuclear antigen (PCNA)) and immunostaining (macrophage, 
      lymphocyte, PCNA). RESULTS: SIMV did not prevent the development of severe 
      hypertension or albuminuria. SIMV-treated animals had less severe renal 
      interstitial inflammation and cell proliferation. MCP-1 expression was 
      significantly diminished in the SIMV-treated animals (55.4 +/- 7.3 vs. 84.4 +/- 
      8.2 OD, p = 0.02). mRNA renal expression for p27 and TGF-beta did not change 
      between groups, but p21 mRNA renal expression, highly induced in this model, 
      significantly decreased with SIMV treatment (31.6 +/- 6.6 vs. 50.2 +/- 5.8 OD, p 
      < 0.05). The interstitial fibrosis score significantly decreased with SIMV (2.46 
      +/- 0.40 vs. 4.07 +/- 0.38%, p < 0.01), which was confirmed by a decrease in 
      renal collagen I and fibronectin expression. Serum cholesterol level did not 
      change with SIMV. CONCLUSION: SIMV attenuated interstitial fibrosis associated 
      with this model of hypertensive renal disease. The mechanism involved MCP-1 
      downregulation. SIMV treatment was also associated with a p21 downregulation in 
      the kidney, which might be involved in the protection of renal scarring.
CI  - Copyright 2005 S. Karger AG, Basel.
FAU - Vieira, J M Jr
AU  - Vieira JM Jr
AD  - Internal Medicine, Renal Division, University of Sao Paulo, Sao Paulo, Brazil. 
      josemvjr@usp.br
FAU - Rodrigues, L T
AU  - Rodrigues LT
FAU - Mantovani, E
AU  - Mantovani E
FAU - Delle, H
AU  - Delle H
FAU - Mattar, A L
AU  - Mattar AL
FAU - Malheiros, D M A C
AU  - Malheiros DM
FAU - Noronha, I L
AU  - Noronha IL
FAU - Fujihara, C K
AU  - Fujihara CK
FAU - Zatz, R
AU  - Zatz R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050819
PL  - Switzerland
TA  - Nephron Physiol
JT  - Nephron. Physiology
JID - 101159772
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transforming Growth Factor beta)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
RN  - 451W47IQ8X (Sodium Chloride)
RN  - AGG2FN16EV (Simvastatin)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
SB  - IM
MH  - Albuminuria/immunology/pathology
MH  - Animals
MH  - Cell Division
MH  - Chemokine CCL2/genetics/metabolism
MH  - Cyclin-Dependent Kinase Inhibitor p21/metabolism
MH  - Cyclin-Dependent Kinase Inhibitor p27/metabolism
MH  - Disease Models, Animal
MH  - Enzyme Inhibitors/pharmacology
MH  - Extracellular Matrix/physiology
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology
MH  - Hypertension, Renal/*drug therapy/immunology/*pathology
MH  - Lymphocytes/metabolism/pathology
MH  - Macrophages/metabolism/pathology
MH  - Male
MH  - NG-Nitroarginine Methyl Ester/pharmacology
MH  - Nitric Oxide Synthase/antagonists & inhibitors
MH  - RNA, Messenger/analysis
MH  - Rats
MH  - Rats, Wistar
MH  - Simvastatin/*pharmacology
MH  - Sodium Chloride/pharmacology
MH  - Transforming Growth Factor beta/genetics
EDAT- 2005/08/23 09:00
MHDA- 2006/05/25 09:00
CRDT- 2005/08/23 09:00
PHST- 2004/09/30 00:00 [received]
PHST- 2005/05/06 00:00 [accepted]
PHST- 2005/08/23 09:00 [pubmed]
PHST- 2006/05/25 09:00 [medline]
PHST- 2005/08/23 09:00 [entrez]
AID - 87576 [pii]
AID - 10.1159/000087576 [doi]
PST - ppublish
SO  - Nephron Physiol. 2005;101(4):p82-91. doi: 10.1159/000087576. Epub 2005 Aug 19.