Yokota Atsuko, Gamoh Shuji, Tanaka-Totoribe Naoko, Shiba Tatsuo, Kuwabara Masachika, Nakamura Eisaku, Hayase Takahiro, Hisa Hiroaki, Nakamura Kunihide, Yamamoto Ryuichi
Department of Cardiovascular Surgery, Miyazaki Prefectural Nobeoka Hospital, Nobeoka 882-0835, Japan.
Department of Surgery, Faculty of Medicine, Miyazaki University, Miyazaki 889-1692, Japan.
Biochem Biophys Rep. 2016 Mar 17;6:82-87. doi: 10.1016/j.bbrep.2016.03.008. eCollection 2016 Jul.
Diabetes mellitus (DM) is an important risk factor for adverse outcomes of coronary artery bypass grafting. The bypass grafts harvested from patients with DM tend to go into spasm after their implantation into the coronary circulation. To clarify the contribution of 5-hydroxytriptamine (5-HT) and angiotensin II (AngII) in the bypass graft spasm, we examined the contractile reactivity to 5-HT or AngII of isolated human endothelium-denuded saphenous vein (SV) harvested from DM and non-DM patients. The 5-HT-induced constriction of the SV was significantly augmented in the DM group than in the non-DM group, which is similar to our previous report. AngII-induced constriction of the SV was also significantly augmented in the DM group than the non-DM group. Especially in the non-DM group, the AngII-induced maximal vasoconstriction was markedly lower than the 5-HT-induced one. Meanwhile, the increasing rates of AngII-induced vasoconstriction in the DM group to the non-DM group were significantly greater than those of 5-HT-induced vasoconstriction. These results indicate that 5-HT is a potent inducer of SV graft spasm in both DM and non-DM patients, while AngII is a potent inducer of SV graft spasm only in patients with DM. Furthermore, the protein level of AngII AT receptor (ATR), but not the protein level of 5-HT receptor, in the membrane fraction of the SV smooth muscle cells of DM patients was significantly increased as compared with that of the non-DM patients. These results suggest that the mechanism for hyperreactivity to AngII in the SV from DM patients is due to, at least in part, the increase in the amount of ATR on membrane of the SV smooth muscle cells.
糖尿病(DM)是冠状动脉旁路移植术不良预后的重要危险因素。从糖尿病患者获取的旁路移植物植入冠状动脉循环后往往会发生痉挛。为阐明5-羟色胺(5-HT)和血管紧张素II(AngII)在旁路移植物痉挛中的作用,我们检测了从糖尿病患者和非糖尿病患者获取的离体人去内皮大隐静脉(SV)对5-HT或AngII的收缩反应性。与我们之前的报告相似,糖尿病组中5-HT诱导的SV收缩明显强于非糖尿病组。糖尿病组中AngII诱导的SV收缩也明显强于非糖尿病组。特别是在非糖尿病组中,AngII诱导的最大血管收缩明显低于5-HT诱导的最大血管收缩。同时,糖尿病组中AngII诱导的血管收缩相对于非糖尿病组的增加率明显大于5-HT诱导的血管收缩增加率。这些结果表明,5-HT是糖尿病患者和非糖尿病患者SV移植物痉挛的强效诱导剂,而AngII仅是糖尿病患者SV移植物痉挛的强效诱导剂。此外,与非糖尿病患者相比,糖尿病患者SV平滑肌细胞膜部分中AngII AT受体(ATR)的蛋白水平显著升高,而5-HT受体的蛋白水平没有升高。这些结果表明,糖尿病患者SV对AngII反应性过高的机制至少部分是由于SV平滑肌细胞膜上ATR数量的增加。