Simvastatin and Tempol Protect Against Endothelial Dysfunction and Renal Injury in a Model of Obesity and Hypertension

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)