Attenuation of vascular/neural dysfunction in Zucker rats treated with enalapril or rosuvastatin
Attenuation of vascular/neural dysfunction in Zucker rats treated with enalapril or rosuvastatin
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DOI：
10.1038/oby.2007.19
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发表时间：
2008-01-01
期刊：
影响因子：
6.9
通讯作者：
Yorek, Mark A.
中科院分区：
文献类型：
--
作者：
Oltman, Christine L.;Davidson, Eric P.;Yorek, Mark A.
目的：肥胖Zucker大鼠是代谢综合征的动物模型，其发生与高血糖无关的糖尿病样神经病变。本研究的目的是确定是否用于治疗代谢综合征心血管功能障碍的药物也保护神经functions.Methods和程序：肥胖Zucker大鼠在20周龄进行了治疗12周，依那普利或瑞舒伐他汀。瘦大鼠用作对照。通过视频显微镜测量神经外膜小动脉的血管舒张。结果：依那普利治疗可降低血清血管紧张素转换酶（ACE）活性，两种药物均可降低血清胆固醇水平。在32周龄的肥胖Zucker大鼠中，动脉和神经外膜小动脉中的超氧化物水平升高，而用任一种药物治疗则降低。神经外膜小动脉的硝基酪氨酸水平升高，依那普利治疗后降低。EBF降低，并通过任一药物治疗进行纠正。运动神经传导速度降低，依那普利治疗后明显改善。肥胖Zucker大鼠在热刺激反应痛觉减退，这是显着改善与治疗。治疗与依那普利或瑞舒伐他汀显着逆转乙酰胆碱介导的血管舒张的神经外膜小动脉在肥胖Zucker rates.Discussion的减少：即使肥胖Zucker大鼠有正常的血管和神经功能障碍，随着年龄的发展，可以改善治疗与依那普利或瑞舒伐他汀。
Objective: Obese Zucker rats, animal model for the metabolic syndrome, develop a diabetes-like neuropathy that is independent of hyperglycemia. The purpose of this study was to determine whether drugs used to treat cardiovascular dysfunction in metabolic syndrome also protect nerve function.Methods and Procedures: Obese Zucker rats at 20 weeks of age were treated for 12 weeks with enalapril or rosuvastatin. Lean rats were used as controls. Vasodilation in epineurial arterioles was measured by videomicroscopy. Endoneurial blood flow (EBF) was measured by hydrogen clearance and nerve conduction velocity was measured following electrical stimulation of motor or sensory nerves.Results: Enalapril treatment decreased serum angiotensin-converting enzyme (ACE) activity and both drugs reduced serum cholesterol levels. In obese Zucker rats at 32 weeks of age superoxide levels were elevated in the aortas and epineurial arterioles, which were reduced by treatment with either drug. Nitrotyrosine levels were increased in epineurial arterioles and reduced with enalapril treatment. EBF was decreased and corrected by treatment with either drug. Motor nerve conduction velocity was decreased and significantly improved with enalapril treatment. Obese Zucker rats were hypoalgesic in response to a thermal stimulus and this was significantly improved with either treatment. Treatment with either enalapril or rosuvastatin significantly reversed the decrease in acetylcholine-mediated vascular relaxation of epineurial arterioles in obese Zucker rats.Discussion: Even though obese Zucker rats have normal glycemia vascular and neural dysfunctions develop with age and can be improved by treatment with either enalapril or rosuvastatin.