title: Olmesartan ameliorates renovascular injury and oxidative stress in Zucker obese rats enhanced by dietary protein.
abstract: BACKGROUND
  The metabolic syndrome is a risk factor for the development of renal and vascular complications. Dietary protein intake aggravates renal injury in Zucker obese rats, a model of the metabolic syndrome. This study investigated whether dietary protein intake enhances renal and vascular injuries by oxidative stress, and assessed effects of olmesartan, an angiotensin II type 1 receptor blocker, in this model.
  
  
  METHODS
  Zucker obese rats were fed either a standard protein diet, high protein diet (OHP), or high protein diet containing olmesartan or hydralazine for 12 weeks. We examined the glomerulosclerosis score, endothelium-dependent relaxation response in the aorta, 4-hydroxy-2-nonenal (HNE) contents in the kidney and aorta, and mRNA expression of NAD(P)H oxidase components (p22phox and p47phox) in the renal cortex.
  
  
  RESULTS
  The OHP rats developed proteinuria, glomerulosclerosis, and endothelial dysfunction. Olmesartan prevented the development of all these damages in OHP rats, whereas hydralazine improved only glomerulosclerosis. The high protein diet also augmented HNE accumulation in glomeruli, renal arteries, and aortas, and increased the mRNA expressions of p22phox and p47phox in the renal cortex in obese rats. Olmesartan, but not hydralazine, inhibited all these changes.
  
  
  CONCLUSIONS
  These results suggested that increased dietary protein intake exacerbates renal and vascular injuries, and augments oxidative stress in a rat model of the metabolic syndrome. Olmesartan ameliorated these injuries, presumably through its antioxidative effects, whereas hydralazine improved only glomerulosclerosis through its antihypertensive action. Dietary protein-enhanced injuries in the metabolic syndrome may be associated with hypercholesterolemia and the activated renin-angiotensin system.
authors: Division of Nephrology, Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Japan.
authors: Tamehachi
authors: T
authors: Namikoshi
authors: Naruya
authors: N
authors: Tomita
authors: Minoru
authors: M
authors: Satoh
authors: Yoshisuke
authors: Y
authors: Haruna
authors: Shinya
authors: S
authors: Kobayashi
authors: Norio
authors: N
authors: Komai
authors: Tamaki
authors: T
authors: Sasaki
authors: Naoki
authors: N
authors: Kashihara
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D004044:Dietary Proteins / Q000009:adverse effects*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000503:physiopathology; D006830:Hydralazine / Q000494:pharmacology; D006978:Hypertension, Renovascular / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D007093:Imidazoles / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D019255:NADPH Oxidases / Q000378:metabolism; D009765:Obesity / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011924:Rats, Zucker; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D000447:Aldehydes; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D004044:Dietary Proteins; D007093:Imidazoles; D013777:Tetrazoles; D006830:Hydralazine; C437965:olmesartan; D019255:NADPH Oxidases; C515768:Cyba protein, rat; C060505:neutrophil cytosolic factor 1; C027576:4-hydroxy-2-nonenal