罗亚
脐静脉
去甲肾上腺素
血管内皮生长因子受体
静脉
细胞生物学
内分泌学
内科学
化学
癌症研究
生物
医学
信号转导
生物化学
体外
多巴胺
作者
Yumi Seya,Takuya Fukuda,Kazumasa Isobe,Yasushi Kawakami,Kazuhiro Takekoshi
标识
DOI:10.1016/j.ejphar.2006.09.048
摘要
Norepinephrine is a well known major vasoconstricting factor. Recent reports suggest that norepinephrine, in addition to acting as a vasoconstricting factor, may also play several additional roles in endothelial cells. These include: 1] induction of NO release. It has been demonstrated that a small GTP-binding protein, Rho, and its downstream effecter, Rho kinase (ROCK), negatively regulate endothelial nitric oxide synthase (eNOS) production. However, it is not known whether ROCK is directly involved in norepinephrine-induced NO release. 2] Norepinephrine is reported to induce a mitogenic effect, but whether MAPKs are involved in this process is unknown. 3] Recently, we demonstrated an increase in vascular endothelial growth factor (VEGF) mRNA/protein expression in human pheochromocytoma tissue in comparison to normal adrenomedullary tissue. Thus, it is reasonable to speculate that norepinephrine may stimulate the level of VEGF mRNA. The aim of the present study was to clarify the role of norepinephrine and related endothelial adrenoceptor systems in various pathophysiological conditions, such as hypertension and in particular pheochromocytoma, using human umbilical vein endothelial cells (HUVEC). Norepinephrine-induced RhoA attenuation, through cAMP/protein kinase A (PKA) activation coupled with β-adrenoceptors, may lead to eNOS activation in acute conditions. Norepinephrine stimulates the production of VEGF mRNA through cAMP/PKA activation coupled with β-adrenoceptors. Norepinephrine stimulates a mitogenic effect through ERK activation coupled with the α1-adrenoceptor. In conclusion, norepinephrine stimulates eNOS activity via RhoA attenuation, VEGF mRNA synthesis and mitogenic activity in endothelial cells. We propose that an excess of norepinephrine can lead to endothelial dysfunction due to these aforementioned processes.
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