Effects of cisplatin on the contractile function of thoracic aorta of Sprague-Dawley rats

被引:14
作者
Jiang, Ying [1 ,2 ]
Shan, Shigang [1 ,3 ]
Gan, Tieer [1 ]
Zhang, Xiaoyun [1 ]
Lu, Xianghong [4 ]
Hu, Hu [5 ]
Wu, Yihua [1 ]
Sheng, Jianzhong [5 ]
Yang, Jun [1 ,3 ]
机构
[1] Zhejiang Univ, Affiliated Hosp 1, State Key Lab Diag & Treatment Infect Dis, 79 Qingchun Rd, Hangzhou 310003, Zhejiang, Peoples R China
[2] Ctr Testing Int Corp, Suzhou Biol Technol Co Ltd, Kunshan 215300, Jiangsu, Peoples R China
[3] Hangzhou Normal Univ, Sch Publ Hlth, Dept Toxicol, Hangzhou 310036, Zhejiang, Peoples R China
[4] Lishui Peoples Hosp, Dept Pharm, Lishui, Zhejiang 323000, Peoples R China
[5] Zhejiang Univ, Sch Med, Dept Pathol & Pathophysiol, Hangzhou 310058, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
DNA damage; cisplatin; cardiovascular toxicity; vascular contraction;
D O I
10.3892/br.2014.349
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
DNA-damaging agents have been reported to be associated with cardiovascular complications, however, the underlying mechanisms remain to be clarified. In the present study, the possible vascular effects of cisplatin was assessed by measuring its effects on the contractile function of thoracic aortic rings dissected from Sprague-Dawley (SD) rats. Contraction of the aortic ring was induced by 60 mM KCl or 10(-6) M phenylephrine (PE) in an ex vivo perfusion system. Cisplatin (200 mu M) counteracted KCl-and PE-induced contraction by 57.6 and 91.8%, respectively, in endothelium-intact aortic rings. Similar results were obtained in endothelium-denuded aortas. Electromicroscopy analysis revealed severe damage to blood vessel walls in vivo by cisplatin. In addition, cisplatin significantly inhibited adenosine triphosphate (ATP) - induced intracellular Ca2+ concentration ([Ca2+](i)) increases in human umbilical vein endothelial cells (HUVECs). These results suggested that the DNA-damaging agent cisplatin can affect the contractile function of thoracic aortas. In addition, in accordance with its DNA-damaging properties, the cardiovascular toxicity of cisplatin may be the result of its direct cytotoxicity.
引用
收藏
页码:893 / 897
页数:5
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