Both 5-hydroxytryptamine 5-HT2A and 5-HT1B receptors are involved in the vasoconstrictor response to 5-HT in the human isolated internal thoracic artery
Both 5-hydroxytryptamine 5-HT2A and 5-HT1B receptors are involved in the vasoconstrictor response to 5-HT in the human isolated internal thoracic artery
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DOI：
10.1111/j.1440-1681.2008.04933.x
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发表时间：
2008-07-01
影响因子：
2.9
通讯作者：
Yamamoto, Ryuichi
中科院分区：
文献类型：
--
作者：
Tanaka, Naoko;Nakamura, Eisaku;Yamamoto, Ryuichi
1. 经常用作动脉移植物的人胸内动脉 (ITA) 介导血管收缩的 5-羟色胺 (5-HT，血清素) 受体亚型仍不清楚。本研究的目的是阐明负责 5-HT 诱导的人类 ITA 收缩的 5-HT 受体亚型。2。检查了从接受冠状动脉搭桥手术的患者获得的去内皮的人 ITA 对 5-HT 的收缩反应。此外，我们还研究了沙格雷酯和SB224289（分别是5-HT（2A）和5-HT（1B）受体拮抗剂）对5-HT诱导的血管收缩的影响。最后对人ITA中的5-HT(2A)和5-HT(1B)受体进行免疫标记。 3． 5-羟色胺（1 nmol/L-10 mmol/L）以浓度依赖性方式引起血管收缩。沙格雷酯(1 mmol/L)和SB224289 (1 mmol/L)均显着但不完全抑制5-HT诱导的血管收缩。4．相反，同时用超高浓度（均为1 mmol/L）沙格雷酯和SB224289进行预处理几乎完全抑制了5-HT诱导的血管收缩。5．在人 ITA.6 的平滑肌细胞中检测到 5-HT(2A) 和 5-HT(1B) 受体的免疫阳性染色。这些结果表明，在人ITA中，5-HT诱导的血管收缩是通过5-HT(2A)和5-HT(1B)受体的激活介导的。因此，当人ITA用作动脉移植物时，5-HT(2A)和5-HT(1B)受体拮抗剂的组合似乎对于预防5-HT诱导的血管痉挛最有用。
1. The 5-hydroxytryptamine (5-HT, serotonin) receptor subtypes that mediate vasoconstriction in the human internal thoracic artery (ITA), which is frequently used as an arterial graft, remain unclear. The aim of the present study was to elucidate the 5-HT receptor subtypes responsible for 5-HT-induced contraction of the human ITA.2. The contractile responses to 5-HT of endothelium-denuded human ITA obtained from patients undergoing coronary bypass surgery were examined. In addition, we investigated the effects of sarpogrelate and SB224289, antagonists of 5-HT(2A) and 5-HT(1B) receptors, respectively, on the 5-HT-induced vasoconstriction. Finally, 5-HT(2A) and 5-HT(1B) receptors in the human ITA were immunolabelled.3. 5-Hydroxytryptamine (1 nmol/L-10 mmol/L) caused vasoconstriction in a concentration-dependent manner. Both sarpogrelate (1 mmol/L) and SB224289 (1 mmol/L) significantly, but not completely, inhibited 5-HT-induced vasoconstriction.4. Conversely, simultaneous pretreatment with supramaximum concentrations (1 mmol/L for both) of sarpogrelate and SB224289 almost completely inhibited the 5-HT-induced vasoconstriction.5. Immunopositive staining for 5-HT(2A) and 5-HT(1B) receptors was detected in smooth muscle cells of the human ITA.6. These results demonstrate that, in human ITA, 5-HT-induced vasoconstriction is mediated by activation of both 5-HT(2A) and 5-HT(1B) receptors. Thus, when the human ITA is used as an arterial graft, a combination of 5-HT(2A) and 5-HT(1B) receptor antagonists would appear to be most useful to prevent 5-HT-induced vasospasm.