PMID- 19906952
OWN - NLM
STAT- MEDLINE
DCOM- 20100111
LR  - 20220311
IS  - 1522-1466 (Electronic)
IS  - 1931-857X (Print)
IS  - 1522-1466 (Linking)
VI  - 298
IP  - 1
DP  - 2010 Jan
TI  - Simvastatin and tempol protect against endothelial dysfunction and renal injury 
      in a model of obesity and hypertension.
PG  - F86-94
LID - 10.1152/ajprenal.00351.2009 [doi]
AB  - Obesity and hypertension are risk factors for the development of chronic kidney 
      disease. The mechanisms by which elevated blood pressure and fatty acids lead to 
      the development of renal injury are incompletely understood. Here, we 
      investigated the contributions of cholesterol and oxidative stress to renal 
      endothelial dysfunction and glomerular injury in a model of obesity and 
      hypertension. Male Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats 
      (SHR) were fed a normal diet, a high-fat diet, a high-fat diet with tempol, or a 
      high-fat diet with simvastatin for up to 10 wk. Blood pressure was not altered by 
      a high-fat diet or treatments. After 3 wk, renal afferent dilatory responses to 
      acetylcholine were impaired in WKY rats and SHR fed a high-fat diet. Tempol 
      treatment prevented this vascular dysfunction in both strains; however, 
      simvastatin treatment demonstrated greater beneficial effects in the SHR. 
      Albuminuria was observed in the SHR and was exacerbated by a high-fat diet. 
      Tempol and simvastatin treatment significantly ameliorated albuminuria in the SHR 
      fed a high-fat diet. Ten weeks on a high-fat resulted in an increase in urinary 
      8-isoprostane in WKY rats and SHR, and tempol and simvastatin treatment prevented 
      this increase, indicating a reduction in renal oxidative stress. Monocyte 
      chemoattractant protein-1 (MCP-1) excretion was significantly elevated by a 
      high-fat diet in both strains, and tempol prevented this increase. Interestingly, 
      simvastatin treatment had no effect on MCP-1 levels. These data indicate that 
      tempol and simvastatin treatment via a reduction in oxidative stress improve 
      renal endothelial function and decrease glomerular injury in a model of obesity 
      and hypertension.
FAU - Knight, Sarah F
AU  - Knight SF
AD  - Vascular Biology Center, Medical College of Georgia, Augusta, Georgia, USA.
FAU - Yuan, Jianghe
AU  - Yuan J
FAU - Roy, Siddhartha
AU  - Roy S
FAU - Imig, John D
AU  - Imig JD
LA  - eng
GR  - R01 HL059699/HL/NHLBI NIH HHS/United States
GR  - R01 HL059699-11/HL/NHLBI NIH HHS/United States
GR  - HL59699/HL/NHLBI NIH HHS/United States
GR  - DK38266/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20091111
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Antioxidants)
RN  - 0 (Cyclic N-Oxides)
RN  - 0 (Dietary Fats)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Spin Labels)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - AGG2FN16EV (Simvastatin)
RN  - U78ZX2F65X (tempol)
SB  - IM
MH  - Albuminuria/metabolism/prevention & control
MH  - Animals
MH  - Antioxidants/therapeutic use
MH  - Cholesterol/blood
MH  - Cyclic N-Oxides/*therapeutic use
MH  - Dietary Fats/adverse effects
MH  - Disease Models, Animal
MH  - Endothelium, Vascular/*physiopathology
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
MH  - Hypertension/*complications/metabolism
MH  - Kidney Failure, Chronic/epidemiology/metabolism/*prevention & control
MH  - Male
MH  - Obesity/*complications/metabolism
MH  - Oxidative Stress/physiology
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Rats, Inbred WKY
MH  - Risk Factors
MH  - Simvastatin/*therapeutic use
MH  - Spin Labels
PMC - PMC3774183
EDAT- 2009/11/13 06:00
MHDA- 2010/01/12 06:00
PMCR- 2011/01/01
CRDT- 2009/11/13 06:00
PHST- 2009/11/13 06:00 [entrez]
PHST- 2009/11/13 06:00 [pubmed]
PHST- 2010/01/12 06:00 [medline]
PHST- 2011/01/01 00:00 [pmc-release]
AID - 00351.2009 [pii]
AID - F-00351-2009 [pii]
AID - 10.1152/ajprenal.00351.2009 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2010 Jan;298(1):F86-94. doi: 
      10.1152/ajprenal.00351.2009. Epub 2009 Nov 11.