PMID- 18463318
OWN - NLM
STAT- MEDLINE
DCOM- 20080825
LR  - 20211020
IS  - 1931-857X (Print)
IS  - 1522-1466 (Electronic)
IS  - 1522-1466 (Linking)
VI  - 295
IP  - 1
DP  - 2008 Jul
TI  - Renoprotection by statins is linked to a decrease in renal oxidative stress, 
      TGF-beta, and fibronectin with concomitant increase in nitric oxide 
      bioavailability.
PG  - F53-9
LID - 10.1152/ajprenal.00041.2008 [doi]
AB  - Clinical and experimental studies have provided evidence suggesting that statins 
      exert renoprotective effects. To investigate the mechanisms by which statins may 
      exert renoprotection, we utilized the hypertensive Dahl salt-sensitive (DS) rat 
      model, which manifests cardiovascular and renal injury linked to increased 
      angiotensin II-dependent activation of NADPH oxidase and decreased nitric oxide 
      (NO) bioavailability. DS rats given high salt diet (4% NaCl) for 10 wk exhibited 
      hypertension [systolic blood pressure (SBP) 200 +/- 8 vs. 150 +/- 2 mmHg in 
      normal salt diet (0.5% NaCl), P < 0.05], glomerulosclerosis, and proteinuria 
      (158%). This was associated with increased renal oxidative stress demonstrated by 
      urinary 8-F(2alpha)-isoprostane excretion and NADPH oxidase activity, increased 
      protein expression of transforming growth factor (TGF)-beta (63%) and fibronectin 
      (181%), increased mRNA expression of the proinflammatory molecules monocyte 
      chemoattractant protein-1 (MCP-1) and lectin-like oxidized LDL receptor-1 
      (LOX-1), as well as downregulation of endothelial NO synthase (eNOS) activity 
      (-44%) and protein expression. Return to normal salt had no effect on SBP or any 
      of the measured parameters. Atorvastatin (30 mg.kg(-1).day(-1)) significantly 
      attenuated proteinuria and glomerulosclerosis and normalized renal oxidative 
      stress, TGF-beta1, fibronectin, MCP-1 and LOX-1 expression, and eNOS activity and 
      expression. Atorvastatin-treated rats showed a modest reduction in SBP that 
      remained in the hypertensive range (174 +/- 8 mmHg). Atorvastatin combined with 
      removal of high salt normalized SBP and proteinuria. These findings suggest that 
      statins mitigate hypertensive renal injury by restoring the balance among NO, 
      TGF-beta1, and oxidative stress and explain the added renoprotective effects 
      observed in clinical studies using statins in addition to inhibitors of the 
      renin-angiotensin system.
FAU - Zhou, Ming-Sheng
AU  - Zhou MS
AD  - Nephrology-Hypertension Section, Veterans Affairs Medical Center, Vascular 
      Biology Institute, University of Miami Miller School of Medicine, Miami, FL 
      33125, USA. mzhou2@med.miami.edu
FAU - Schuman, Ivonne Hernandez
AU  - Schuman IH
FAU - Jaimes, Edgar A
AU  - Jaimes EA
FAU - Raij, Leopoldo
AU  - Raij L
LA  - eng
GR  - DK-069372/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20080507
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Fibronectins)
RN  - 0 (Heptanoic Acids)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Pyrroles)
RN  - 0 (RNA, Messenger)
RN  - 0 (Scavenger Receptors, Class E)
RN  - 0 (Transforming Growth Factor beta)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - A0JWA85V8F (Atorvastatin)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.14.13.39 (Nos3 protein, rat)
RN  - EC 1.6.3.- (NADPH Oxidases)
SB  - IM
MH  - Animals
MH  - Atorvastatin
MH  - Biological Availability
MH  - Blood Pressure/drug effects
MH  - Chemokine CCL2/metabolism
MH  - Fibronectins/*metabolism
MH  - Heptanoic Acids/*pharmacology
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology/therapeutic use
MH  - Kidney/drug effects/pathology/*physiology
MH  - Kidney Failure, Chronic/*prevention & control
MH  - NADPH Oxidases/metabolism
MH  - Nitric Oxide/*physiology
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Nitric Oxide Synthase Type III
MH  - Oxidative Stress/*drug effects
MH  - Proteinuria/urine
MH  - Pyrroles/*pharmacology
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Inbred Dahl
MH  - Scavenger Receptors, Class E/metabolism
MH  - Transforming Growth Factor beta/*metabolism
PMC - PMC2494511
EDAT- 2008/05/09 09:00
MHDA- 2008/08/30 09:00
PMCR- 2009/07/01
CRDT- 2008/05/09 09:00
PHST- 2008/05/09 09:00 [pubmed]
PHST- 2008/08/30 09:00 [medline]
PHST- 2008/05/09 09:00 [entrez]
PHST- 2009/07/01 00:00 [pmc-release]
AID - 00041.2008 [pii]
AID - F-00041-2008 [pii]
AID - 10.1152/ajprenal.00041.2008 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2008 Jul;295(1):F53-9. doi: 
      10.1152/ajprenal.00041.2008. Epub 2008 May 7.