Tetramethylpyrazine inhibits angiotensin II-increased NAD(P)H oxidase activity and subsequent proliferation in rat aortic smooth muscle cells.
Tetramethylpyrazine (TMP) is the major component extracted from the Chinese herb, Chuanxiong, which is widely used in China for the treatment of cardiovascular problems. The aims of this study were to examine whether TMP may alter angiotenisn II (Ang II)-induced proliferation and to identify the putative underlying signaling pathways in rat aortic smooth muscle cells. Cultured rat aortic smooth muscle cells were preincubated with TMP and then stimulated with Ang II, [3H]-thymidine incorporation and the ET-1 expression was examined. Ang II increased DNA synthesis which was inhibited by TMP (1-100 microM). TMP inhibited the Ang II-induced ET-1 mRNA levels and ET-1 secretion. TMP also inhibited Ang II-increased NAD(P)H oxidase activity, intracellular reactive oxygen species (ROS) levels, and the ERK phosphorylation. Furthermore, TMP and antioxidants such as Trolox and diphenylene iodonium decreased Ang II-induced ERK phosphorylation, and activator protein-1 reporter activity. In summary, we demonstrate for the first time that TMP inhibits Ang II-induced proliferation and ET-1, partially by interfering with the ERK pathway via attenuation of Ang II-increased NAD(P)H oxidase and ROS generation. Thus, this study delivers important new insight in the molecular pathways that may contribute to the proposed beneficial effects of TMP in cardiovascular disease.
Wong
Kar-Lok
KL
Department of Anesthesiology, Pain Management and Critical Care Medicine, China Medical University and Hospital, Taichung, Taiwan.
Wu
King-Chuen
KC
Wu
Rick Sai-Chuen
RS
Chou
Yu-Hsiang
YH
Cheng
Tzu-Hurng
TH
Hong
Hong-Jye
HJ
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D019332:Endothelin-1 / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D019255:NADPH Oxidases / Q000187:drug effects / Q000378:metabolism*; D011719:Pyrazines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*
D019332:Endothelin-1; D011719:Pyrazines; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D014665:Vasodilator Agents; D000804:Angiotensin II; D004247:DNA; D019255:NADPH Oxidases; D048049:Extracellular Signal-Regulated MAP Kinases; C017953:tetramethylpyrazine