Saphenous vein (SV) is one of the most widely used graft material in patients undergoing coronary artery bypass graft surgery (CABG). Thromboxane A₂ (TXA₂) is implicated in graft failure by inducing vasoconstriction and platelet aggregation. The aim of this study is to investigate the mechanism involved in TXA₂-induced vasoconstriction in human SV. The role of different inhibitors and blockers on U46619 (TXA₂-mimetic)-induced vasoconstriction is investigated by using an isolated organ bath system. Relaxation responses to several mediators are evaluated in SV pre-contracted with U46619 and compared with those pre-contracted with phenylephrine. Our results demonstrate that U46619-induced contraction is completely blocked by myosin light chain kinase inhibitor ML-9 or TP receptor antagonist BAY u3405. Furthermore, U46619-induced contraction is partially inhibited by phospholipase C inhibitor U73122, protein kinase C inhibitor calphostin C, Rho-kinase inhibitor Y-27632, L-type calcium channel blocker nifedipine, store-operated channel inhibitor SKF96365 or removal of extracellular calcium. Relaxation responses to NO donor (sodium nitroprusside), guanylate cyclase (GC) stimulator (riociguat), phosphodiesterase (PDE) inhibitors (sildenafil, IBMX), adenylate cyclase (AC) activator (forskolin) and acetylcholine (ACh) are markedly reduced when U46619 is used as a pre-contraction agent. Our results demonstrate that influx of extracellular Ca²⁺ (through L-type calcium channels and store-operated calcium channels) and intracellular Ca²⁺ release together with Ca²⁺ sensitization (through Rho-kinase activation) are necessary components for TXA₂-induced vasoconstriction in SV. Moreover, more pronounced decrease in vasorelaxation induced by several mediators (SNP, riociguat, sildenafil, IBMX, forskolin, and ACh) in the presence of U46619 when compared with phenylephrine suggests that there is a crosstalk between the TP receptor signaling pathway and PDE, AC, GC enzymes. We believe that the investigation of mechanism of the TXA₂-induced vasoconstriction in SV will provide additional information for the prevention of SV graft failure.

大隐静脉 (SV) 是接受冠状动脉搭桥手术 (CABG) 的患者最广泛使用的移植材料之一。血栓素 A ₂ (TXA ₂ ) 通过诱导血管收缩和血小板聚集与移植失败有关。本研究的目的是研究 TXA ₂诱导人 SV 血管收缩的机制。不同抑制剂和阻滞剂对 U46619 (TXA ₂-模拟）诱导的血管收缩通过使用离体器官浴系统进行研究。在与 U46619 预先收缩的 SV 中评估对几种介质的松弛反应，并与那些与去氧肾上腺素预先收缩的反应进行比较。我们的结果表明 U46619 诱导的收缩被肌球蛋白轻链激酶抑制剂 ML-9 或 TP 受体拮抗剂 BAY u3405 完全阻断。此外，U46619 诱导的收缩受到磷脂酶 C 抑制剂 U73122、蛋白激酶 C 抑制剂钙磷蛋白 C、Rho 激酶抑制剂 Y-27632、L 型钙通道阻滞剂硝苯地平、存储操作通道抑制剂 SKF96365 或去除细胞外钙的部分抑制。对 NO 供体（硝普钠）、鸟苷酸环化酶（GC）刺激物（riociguat）、磷酸二酯酶（PDE）抑制剂（西地那非、IBMX）的松弛反应，当 U46619 用作预收缩剂时，腺苷酸环化酶 (AC) 激活剂 (forskolin) 和乙酰胆碱 (ACh) 显着减少。我们的结果表明，细胞外 Ca 的流入²⁺（通过L 型钙通道和钙池操纵的钙通道）和细胞内Ca ²⁺释放以及Ca ²⁺致敏（通过Rho-激酶激活）是TXA ₂诱导的SV 血管收缩的必要成分。此外，与去氧肾上腺素相比，在存在 U46619 的情况下，由几种介质（SNP、riociguat、西地那非、IBMX、毛喉素和 ACh）诱导的血管舒张作用更显着降低，这表明 TP 受体信号通路与 PDE、AC 之间存在串扰, GC 酶。我们相信，对 TXA ₂诱导的 SV 血管收缩机制的研究将为预防 SV 移植失败提供额外的信息。