Effects of Benzo(a)pyrene on the Contractile Function of the Thoracic Aorta of Sprague-dawley Rats  

作　　者：GAN Tie Er XIAO Su Ping JIANG Ying HU Hu WU Yi Hua DUERKSEN-HUGHES Penelope J SHENG Jian Zhong YANG Jun 

机构地区：[1]First Affiliated Hospital,State Key Laboratory for Diagnosis and Treatment of Infectious Diseases,Zhejiang University,Hangzhou 310003,Zhejiang,China [2]Department of Pathology and Pathophysiology,Zhejiang University School of Medicine,Hangzhou 310058,Zhejiang,China [3]Department of Basic Science,Division of Biochemistry,Loma Linda University School of Medicine,Loma Linda,CA 92354,USA [4]Department of Toxicology,Hangzhou Normal University School of Public Health,Hangzhou 310036,Zhejiang,China

出　　处：《Biomedical and Environmental Sciences》2012年第5期549-556,共8页生物医学与环境科学（英文版）

基　　金：supported by National Natural Science Foundation of China,grant numbers30872140and81172692;Zhejiang Provincial Natural Science Foundation,R2100555;Ministry of Science and Technology,China,2009DFB30390

摘　　要：Abstract Objective To evaluate the possible vascular effects of an environment carcinogen benzo（a）pyrene （BaP）. Methods The cytotoxicit of BaP and rat liver S9 （0.25 mg/mL）-activated BaP were examined by MTT assay. Thoracic aortic rings were dissected from Sprague-Dawley rats. Contraction of aortic rings was induced by 60 mmol/L KCl or 10-6 mol/L phenylephrine （PE） in an ex-vivo perfusion system after BaP （100 tlmol/L） incubation for 6 h. [Ca^2＋]i was measured using Fluo-4/AM. For in-vivo treatment, rats were injected with BaP for 4 weeks （10 mg/kg, weekly, i.p.）. Results BaP （1-500 μm） did not significantly affect cell viability; S9-activated BaP stimulated cell proliferation. BaP did not affect the contractile function of endothelium-intact or -denuded aortic rings. BaP did not affect ATP-induced （[Ca2＋]i） increases in human umbilical vein endothelial cells. In BaP-treated rats, heart rate and the number of circulating inflammatory cells were not affected. Body weight decreased while blood pressure increased significantly. The maximum aortic contractile responses to PE and KCI and the maximum aortic relaxation response to acetylcholine were significantly decreased by 25.0%, 34.2%, and 10.4%, respectively. Conclusion These results suggest, in accordance with its DNA-damaging properties, that metabolic activation is a prerequisite for BaP-induced cardiovascular toxicity.Abstract Objective To evaluate the possible vascular effects of an environment carcinogen benzo（a）pyrene （BaP）. Methods The cytotoxicit of BaP and rat liver S9 （0.25 mg/mL）-activated BaP were examined by MTT assay. Thoracic aortic rings were dissected from Sprague-Dawley rats. Contraction of aortic rings was induced by 60 mmol/L KCl or 10-6 mol/L phenylephrine （PE） in an ex-vivo perfusion system after BaP （100 tlmol/L） incubation for 6 h. [Ca^2＋]i was measured using Fluo-4/AM. For in-vivo treatment, rats were injected with BaP for 4 weeks （10 mg/kg, weekly, i.p.）. Results BaP （1-500 μm） did not significantly affect cell viability; S9-activated BaP stimulated cell proliferation. BaP did not affect the contractile function of endothelium-intact or -denuded aortic rings. BaP did not affect ATP-induced （[Ca2＋]i） increases in human umbilical vein endothelial cells. In BaP-treated rats, heart rate and the number of circulating inflammatory cells were not affected. Body weight decreased while blood pressure increased significantly. The maximum aortic contractile responses to PE and KCI and the maximum aortic relaxation response to acetylcholine were significantly decreased by 25.0%, 34.2%, and 10.4%, respectively. Conclusion These results suggest, in accordance with its DNA-damaging properties, that metabolic activation is a prerequisite for BaP-induced cardiovascular toxicity.

关 键 词：DNA damage Benzo（a）pyrene Cardiovascular toxicity Vascular contraction 

分 类 号：Q95-331[生物学—动物学] X503.225[环境科学与工程—环境工程]