Serotonin induces vasoconstriction of smooth muscle cell-rich neointima through 5-hydroxytryptamine2A receptor in rabbit femoral arteries
Serotonin induces vasoconstriction of smooth muscle cell-rich neointima through 5-hydroxytryptamine2A receptor in rabbit femoral arteries
复制标题
DOI：
10.1111/j.1538-7836.2008.02996.x
复制
发表时间：
2008-07-01
影响因子：
10.4
通讯作者：
Asada, Y.
中科院分区：
文献类型：
--
作者：
Nishihira, K.;Yamashita, A.;Asada, Y.
背景：平滑肌细胞（SMC）丰富的内膜是在侵蚀斑块和痉挛动脉中观察到的动脉粥样硬化病变的形态学特征。血管内膜富含smc的动脉在某些血管活性药物作用下易发生血管收缩或痉挛。目的：评价富含smc的内膜在血栓性血管收缩中的作用。方法：采用球囊法损伤兔股动脉，建立富含smc的新生内膜，测定其对5-羟色胺（5-HT）、二磷酸腺苷、三磷酸腺苷和凝血酶的等长张力。结果：与未损伤动脉相比，在这些药物中，只有5-HT诱导了富含smc的新生内膜损伤动脉的过度收缩反应。新内膜和介质的平滑肌细胞均表达5-HT2A受体，而选择性5-HT2A受体拮抗剂sarpogreate可显著抑制这种过度收缩。此外，与未损伤的中膜相比，5-HT诱导分离的新生内膜收缩和分离的中膜过度收缩。sarpogreate和fasudil（一种特异性rho激酶抑制剂）可以显著抑制损伤动脉内膜和中膜的收缩。结论：这些结果表明，5-HT在血栓性血管收缩中起着至关重要的作用，富含smc的内膜和介质通过5-HT2A受体和rho激酶途径直接参与动脉粥样硬化血管的超收缩反应。
Background: Smooth muscle cell (SMC)-rich intima is a morphological feature of atherosclerotic lesions that is observed in eroded plaque and spastic arteries. Arteries with SMC-rich intima are susceptible to vasoconstriction or vasospasm against some vasoactive agents. Objective: The present study evaluates the contribution of SMC-rich intima to thrombogenic vasoconstriction. Methods: We established SMC-rich neointima by damaging rabbit femoral arteries using balloons and then measured the isometric tension of the femoral strips against 5-hydroxytryptamine (5-HT), adenosine diphosphate, adenosine triphosphate and thrombin. Results: Among these agents, only 5-HT induced a hypercontractile response of the injured arteries with SMC-rich neointima, compared with non-injured arteries. Smooth muscle cells of both the neointima and media expressed 5-HT2A receptor, and sarpogrelate, a selective 5-HT2A receptor antagonist significantly inhibited the hypercontraction. Furthermore, 5-HT induced contraction of separated neointima and hypercontraction of separated media compared with non-injured media. Sarpogrelate and fasudil, a specific Rho-kinase inhibitor, significantly suppressed such contraction of both the neointima and media of injured arteries. Conclusions: These results suggest that 5-HT plays a crucial role in thrombogenic vasoconstriction, and that SMC-rich intima as well as media directly contributes to the hypercontractile response of atherosclerotic vessels through the 5-HT2A receptor and the Rho-kinase pathway.