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标题：Isoproterenol Inhibits Angiotensin II-Stimulated Proliferation and Reactive Oxygen Species Production in Vascular Smooth Muscle Cells through Heme Oxygenase-1
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作者：Jung Eun Kim ; Young Jin Kang ; Kwang Youn Lee 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2009
卷号：32
期号：6
页码：1047-1052
DOI：10.1248/bpb.32.1047
出版社：The Pharmaceutical Society of Japan
摘要：Heme oxygenase (HO)-1 is a well-known cytoprotectant against oxidative stress and exhibits an antiproliferative effect in vascular smooth muscle cells (VSMCs). The purpose of the present study was to test whether isoproterenol, one of the synthetic catecholamines having β-adrenergic activity, affected angiotensin II (Ang II)-induced cell proliferation and reactive oxygen species (ROS) production. Also, the presumptive underlying signaling pathways in VSMCs were studied. Aortic VSMCs from 11-week-old male Sprague-Dawley rats were used. Isoproterenol dose-dependently increased HO-1 expression through β₂-adrenoceptor (AR) and protein kinase A (PKA) pathway, and isoproterenol concentration-dependently increased β₂-AR mRNA expression. Isoproterenol attenuated Ang II-induced cell proliferation, as evidenced by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay. This effect of isoproterenol was inhibited by pretreatment of the cells with β₂-AR antagonist butoxamine, PKA inhibitor H-89 and HO inhibitor Tin Protoporphyrin IX (SnPP IX), respectively. Isoproterenol inhibited phosphorylation level of Ang II-induced extracellular signal-regulated kinase (ERK1/2). Isoproterenol significantly inhibited Ang II-induced ROS production through the ERK1/2 pathway. These findings suggest that isoproterenol, via induction of HO-1, inhibits Ang II-stimulated proliferation and ROS production in cultured VSMCs.
关键词：heme oxygenase-1;isoproterenol;angiotensin II;reactive oxygen species;β2-adrenoceptor