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Simvastatin and Tempol Protect Against Endothelial Dysfunction and Renal Injury in a Model of Obesity and Hypertension
Author(s) -
Knight Sarah F,
Yuan Jianghe,
Roy Siddhartha,
Imig John D
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.947.8
Subject(s) - endocrinology , medicine , excretion , simvastatin , endothelial dysfunction , obesity , proteinuria , chemistry , kidney
Obesity and hypertension are linked to the development of chronic kidney disease. We investigated fatty acid and superoxide (SO) contribution to endothelial dysfunction and renal injury in a model of obesity and hypertension. Male 8 week old WKY rats and SHR fed normal diet (NFD) (7% fat), high fat diet (HFD) (36% fat), HFD with Tempol (Tmp) (20mg/kg/day) or HFD with Simvastatin (Sim) (10mg/kg/day) up to 10 weeks (n=4). Blood pressure was unaffected by Tmp or Sim treatment. After 3 weeks, renal afferent dilatory responses to acetylcholine reached 75% of baseline diameter in NFD SHR but 47% in HFD SHR (P<0.05). In Tmp and Sim treated SHR diameters reached 79% and 78% of baseline (P<0.05). Ten weeks HFD raised albumin excretion from 199 ± 35 in NFD SHR to 870 ± 378μg/day in HFD SHR (P<0.05), Tmp and Sim treated WKY and SHR excreted just 258 ± 111 and 455 ± 76μg/day, respectively. Urinary 8‐isoprostane increased from 6 ± 2 to 27 ± 13ng/day and 12 ± 4 to 26 ± 9ng/day by HFD in WKY and SHR (P<0.05). Tmp and Sim treatment prevented this increase. Monocyte chemoattractant protein‐1 (MCP‐1) excretion was 29 ± 12 and 40 ± 5ng/day in HFD WKY and SHR compared to 11 ± 3, 15 ± 4, 16 ± 6 and 30 ± 10ng/day in NFD and Tmp WKY and SHR respectively (P<0.05). Sim WKY and SHR excreted 38 ± 7 and 43 ± 9ng/day. This indicates that Tmp and Sim prevent endothelial dysfunction and renal injury in a model of obesity and hypertension via a reduction in SO, independently from MCP‐1. (NIH)