Pioglitazone ameliorates endothelial dysfunction in obese rats with nephropathy.
Endothelial dysfunction is a key event in the development of renovascular complications in the metabolic syndrome. The aim of this study was to elucidate the pathogenetic mechanisms involved in renovascular injuries in the Zucker obese rat, a model of the metabolic syndrome, and to examine the therapeutic effects of pioglitazone, a thiazolidinedione. Obese rats fed high-protein diet (OHP) for 12 weeks exhibited nephropathy and endothelial dysfunction, which were improved by pioglitazone. Accumulation of nitrotyrosine, a tracer of nitrative stress, was increased in aorta of the OHP group. The mRNA expressions of NADPH oxidase components and inducible nitric oxide synthase in the aorta were enhanced in the OHP group. Pioglitazone reduced nitrotyrosine in the aorta of the OHP group, inhibiting the augmented expression levels of both. These results suggest that nitrative stress could cause endothelial dysfunction in the rat model of metabolic syndrome with nephropathy, and that pioglitazone ameliorates these injuries, presumably by reducing nitrative stress.
Division of Nephrology, Department of Internal Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Japan.
Tamehachi
T
Namikoshi
Minoru
M
Satoh
Naruya
N
Tomita
Yoshisuke
Y
Haruna
Shinya
S
Kobayashi
Norio
N
Komai
Tamaki
T
Sasaki
Naoki
N
Kashihara
D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D007674:Kidney Diseases / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications*; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000150:complications*; D000077205:Pioglitazone; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis; D014664:Vasodilation / Q000187:drug effects
D012333:RNA, Messenger; D045162:Thiazolidinediones; C002744:3-nitrotyrosine; D014443:Tyrosine; D019255:NADPH Oxidases; D000077205:Pioglitazone