Effect of rosuvastatin on hyperuricemic rats and the protective effect on endothelial dysfunction.
Endothelial dysfunction plays a key role in the development of cardiovascular diseases, renal injuries and hypertension induced by hyperuricemia. Therapies targeting uric acid (UA) may be beneficial in cardiovascular diseases. In the present study, the effect of rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, was investigated to determine whether rosuvastatin improves endothelial dysfunction via the endothelial nitric oxide (NO) pathway and delays the pathogenesis of endothelial dysfunction in hyperuricemic rats. A total of 72 Sprague-Dawley rats (age, 8 weeks) were randomly divided into six groups (12 rats per group), including the control, model, 2.5 mg/kg/day rosuvastatin, 5 mg/kg/day rosuvastatin, 10 mg/kg/day rosuvastatin and 53.57 mg/kg/day allopurinol groups. The model, rosuvastatin and allopurinol rats were subjected to hyperuricemia, induced by the administration of yeast extract powder (21 g/kg/day) and oxonic acid potassium salt (200 mg/kg/day). The hyperuricemic rats were treated with 2.5, 5.0 or 10.0 mg/kg/day rosuvastatin orally for six weeks, while rats treated with allopurinol (53.57 mg/kg/day) were used as a positive control. The serum levels of NO and the gene expression levels of endothelial NO synthase in the aortic tissue increased, whereas the serum levels of UA, endothelin-1 and angiotensin II decreased in the hyperuricemic rats treated with rosuvastatin, particularly at a high rosuvastatin dose (10 mg/kg/day). In addition, the curative effect of the 10 mg/kg/day rosuvastatin group was evidently higher compared with the allopurinol group. Therefore, rosuvastatin may be a novel drug candidate for the treatment of hyperuricemia due to its endothelial protective properties.
Department of Cardiology, The First Affiliated Hospital, Xinjiang Medical University, Ürümqi, Xinjiang 830011, P.R. China.
Dilidaer
D
Xilifu
Xinjiang Key Laboratory of Molecular Biology and Endemic Diseases, Xinjiang Medical University, Ürümqi, Xinjiang 830011, P.R. China.
Abulizi
A
Abudula
Department of Pathology, School of Basic Medicine, Xinjiang Medical University, Ürümqi, Xinjiang 830011, P.R. China.
Nijiati
N
Rehemu
Department of Cardiology, The First Affiliated Hospital, Xinjiang Medical University, Ürümqi, Xinjiang 830011, P.R. China.
Long
L
Zhao
Department of Cardiology, The First Affiliated Hospital, Xinjiang Medical University, Ürümqi, Xinjiang 830011, P.R. China.
Xinrong
X
Zhou
Department of Cardiology, The First Affiliated Hospital, Xinjiang Medical University, Ürümqi, Xinjiang 830011, P.R. China.
Xiangyang
X
Zhang
endothelial dysfunction; hyperuricemia; nitric oxide; rosuvastatin; uric acid