Effects of cisplatin on the contractile function of thoracic aorta of Sprague-Dawley rats
Effects of cisplatin on the contractile function of thoracic aorta of Sprague-Dawley rats
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顺铂对Sprague-Dawley大鼠胸主动脉收缩功能的影响
DOI：
10.3892/br.2014.349
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发表时间：
2014-11-01
影响因子：
2.3
通讯作者：
Yang, Jun
中科院分区：
文献类型：
--
作者：
Jiang, Ying;Shan, Shigang;Yang, Jun
DNA损伤剂已被报道与心血管并发症有关，然而，其潜在的机制仍有待阐明。在本研究中，通过测量顺铂对SD大鼠胸主动脉环收缩功能的影响来评估其可能的血管效应。在体外灌流系统中，用60 mM氯化钾或10(-6)M苯肾上腺素(PE)诱发主动脉环收缩。在内皮完整的主动脉环上，顺铂(200 MU M)可分别拮抗KCl和PE引起的收缩57.6%和91.8%。在去内皮的主动脉中也得到了类似的结果。电子显微镜分析显示顺铂对体内血管壁有严重损伤。此外，顺铂显著抑制三磷酸腺苷(ATP)诱导的人脐静脉内皮细胞(HUVECs)内钙浓度([Ca~(2+)](I))升高。提示DNA损伤剂顺铂可影响胸主动脉的收缩功能。此外，根据顺铂的DNA损伤特性，顺铂的心血管毒性可能是其直接细胞毒性的结果。
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.