title: Effects of cisplatin on the contractile function of thoracic aorta of Sprague-Dawley rats.
abstract: 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 10-6M phenylephrine (PE) in anex vivoperfusion system. Cisplatin (200 μM) 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 wallsin vivoby 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.
authors.affiliation: The First Affiliated Hospital, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China ; Suzhou Biological Technology Co., Ltd., of Centre Testing International Corporation, Kunshan, Jiangsu 215300, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: The First Affiliated Hospital, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China ; Department of Toxicology, Hangzhou Normal University School of Public Health, Hangzhou, Zhejiang 310036, P.R. China.
authors.forename: Shigang
authors.initials: S
authors.lastname: Shan
authors.affiliation: The First Affiliated Hospital, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Tieer
authors.initials: T
authors.lastname: Gan
authors.affiliation: The First Affiliated Hospital, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Lishui People's Hospital, Lishui, Zhejiang 323000, P.R. China.
authors.forename: Xianghong
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China.
authors.forename: Hu
authors.initials: H
authors.lastname: Hu
authors.affiliation: The First Affiliated Hospital, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Sheng
authors.affiliation: The First Affiliated Hospital, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China ; Department of Toxicology, Hangzhou Normal University School of Public Health, Hangzhou, Zhejiang 310036, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
keywords: DNA damage; cardiovascular toxicity; cisplatin; vascular contraction