Sildenafil restores endothelial function in the apolipoprotein E knockout mouse.
Sildenafil restores endothelial function in the apolipoprotein E knockout mouse.
复制标题
西地那非恢复载脂蛋白E基因敲除小鼠中的内皮功能。
DOI：
10.1186/1479-5876-11-3
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发表时间：
2013-01-05
影响因子：
7.4
通讯作者：
Vasquez EC
中科院分区：
文献类型：
--
作者：
Balarini CM;Leal MA;Gomes IB;Pereira TM;Gava AL;Meyrelles SS;Vasquez EC
动脉粥样硬化是动脉壁的炎症过程，由内皮功能障碍引发，伴随着活性氧（ROS）和一氧化氮（NO）产生的不平衡。西地那非是一种用于勃起功能障碍的选择性磷酸二酯酶-5（PDE 5）抑制剂，通过增强NO的作用发挥其心血管作用。本研究的目的是研究西地那非对载脂蛋白E基因敲除（apoE−/−）小鼠内皮功能和动脉粥样硬化进展的影响。将西地那非（Viagra®，40 mg/kg/天，经口灌胃给药3周）处理的ApoE−/−小鼠与未处理的apoE−/−和野生型（WT）小鼠进行比较。用主动脉环评价各组对乙酰胆碱（ACh）的舒张反应。在一组单独的实验中，NO和ROS在ACh舒张反应中的作用通过用L-NAME（NO合成酶抑制剂）或夹竹桃素（NADPH氧化酶抑制剂）孵育主动脉环来评估。此外，动脉粥样硬化病变进行了量化和超氧化物的生产进行了评估。西地那非恢复了apoE−/−小鼠主动脉环对乙酰胆碱（ACh）的血管舒张反应。用L-NAME治疗在所有三组小鼠中取消了对ACh的血管舒张反应，并显示在西地那非治疗的动物中NO在内皮依赖性血管舒张中的参与增强。西地那非处理的apoE−/−小鼠的正常内皮功能不受夹竹桃苷的影响，突出了这些动物中ROS产生的低水平。此外，形态学分析表明，西地那非治疗导致主动脉斑块沉积减少约40%。这是第一项在自发性高胆固醇血症模型中证明长期西地那非治疗对内皮功能障碍和动脉粥样硬化的有益作用的研究。这些数据表明西地那非对内皮功能有益作用的主要机制似乎涉及NO途径的增强沿着氧化应激的降低。
Atherosclerosis is an inflammatory process of the arterial walls and is initiated by endothelial dysfunction accompanied by an imbalance in the production of reactive oxygen species (ROS) and nitric oxide (NO). Sildenafil, a selective phosphodiesterase-5 (PDE5) inhibitor used for erectile dysfunction, exerts its cardiovascular effects by enhancing the effects of NO. The aim of this study was to investigate the influence of sildenafil on endothelial function and atherosclerosis progression in apolipoprotein E knockout (apoE−/−) mice. ApoE−/− mice treated with sildenafil (Viagra®, 40 mg/kg/day, for 3 weeks, by oral gavage) were compared to the untreated apoE−/− and the wild-type (WT) mice. Aortic rings were used to evaluate the relaxation responses to acetylcholine (ACh) in all of the groups. In a separate set of experiments, the roles of NO and ROS in the relaxation response to ACh were evaluated by incubating the aortic rings with L-NAME (NO synthase inhibitor) or apocynin (NADPH oxidase inhibitor). In addition, the atherosclerotic lesions were quantified and superoxide production was assessed. Sildenafil restored the vasodilator response to acetylcholine (ACh) in the aortic rings of the apoE−/− mice. Treatment with L-NAME abolished the vasodilator responses to ACh in all three groups of mice and revealed an augmented participation of NO in the endothelium-dependent vasodilation in the sildenafil-treated animals. The normalized endothelial function in sildenafil-treated apoE−/− mice was unaffected by apocynin highlighting the low levels of ROS production in these animals. Moreover, morphological analysis showed that sildenafil treatment caused approximately a 40% decrease in plaque deposition in the aorta. This is the first study demonstrating the beneficial effects of chronic treatment with sildenafil on endothelial dysfunction and atherosclerosis in a model of spontaneous hypercholesterolemia. These data indicate that the main mechanism of the beneficial effect of sildenafil on the endothelial function appears to involve an enhancement of the NO pathway along with a reduction in oxidative stress.
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影响因子：
64.5
作者：
Moore KJ;Tabas I
通讯作者：
Tabas I
影响因子：
4.5
作者：
Meyrelles SS;Peotta VA;Pereira TM;Vasquez EC
通讯作者：
Vasquez EC
DOI：
10.1161/01.atv.14.1.133
发表时间：
1994-01-01
期刊：
ARTERIOSCLEROSIS AND THROMBOSIS
影响因子：
--
作者：
NAKASHIMA, Y;PLUMP, AS;ROSS, R
通讯作者：
ROSS, R
DOI：
10.1016/s0735-1097(02)02139-3
发表时间：
2002-10-02
影响因子：
24
作者：
Halcox, JPJ;Nour, KRA;Quyyumi, AA
通讯作者：
Quyyumi, AA
影响因子：
8.7
作者：
d'Uscio, LV;Baker, TA;Katusic, ZS
通讯作者：
Katusic, ZS