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

Jiang,Ying; Shan,Shigang; Gan,Tieer; Zhang,Xiaoyun; Lu,Xianghong; Hu,Hu; Wu,Yihua; Sheng,Jianzhong; Yang,Jun

doi:10.3892/br.2014.349

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

Authors:
- Ying Jiang
- Shigang Shan
- Tieer Gan
- Xiaoyun Zhang
- Xianghong Lu
- Hu Hu
- Yihua Wu
- Jianzhong Sheng
- Jun Yang
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Affiliations: The First Affiliated Hospital, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China, Department of Pharmacy, Lishui People's Hospital, Lishui, Zhejiang 323000, P.R. China, Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China
Published online on: August 19, 2014 https://doi.org/10.3892/br.2014.349
Pages: 893-897

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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 10‑6 M phenylephrine (PE) in an ex vivo perfusion 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 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.

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