Simvastatin and tempol protect against endothelial dysfunction and renal injury in a model of obesity and hypertension. Am J Physiol Renal Physiol 2010 Jan;298(1):F86-94
Date
11/13/2009Pubmed ID
19906952Pubmed Central ID
PMC3774183DOI
10.1152/ajprenal.00351.2009Scopus ID
2-s2.0-74049153900 (requires institutional sign-in at Scopus site) 56 CitationsAbstract
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.
Author List
Knight SF, Yuan J, Roy S, Imig JDMESH terms used to index this publication - Major topics in bold
AlbuminuriaAnimals
Antioxidants
Cholesterol
Cyclic N-Oxides
Dietary Fats
Disease Models, Animal
Endothelium, Vascular
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypertension
Kidney Failure, Chronic
Male
Obesity
Oxidative Stress
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Risk Factors
Simvastatin
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