Kaleli Durman Deniz, Dağtekin Nurdan, Civelek Erkan, İyigün Taner, Teskin Önder, Uydeş Doğan Birsel Sönmez
Department of Pharmacology, Faculty of Pharmacy, Istanbul University, Istanbul 34116, Türkiye.
Department of Cardiovascular Surgery, Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training Research Hospital, Istanbul 34303, Türkiye.
Life (Basel). 2025 Jul 19;15(7):1139. doi: 10.3390/life15071139.
S-nitrosoglutathione (GSNO), a promising S-nitrosothiol, has been recognized for its ability to modulate vascular tone through its vasodilatory, antiplatelet, and antiproliferative effects. However, data on its vasodilatory effects in human vessels remain limited, and its mechanisms of action have yet to be fully elucidated. In this study, we aimed to investigate the vasorelaxant effect of GSNO and its underlying mechanisms, with particular focus on the soluble guanylate cyclase (sGC)/nitric oxide (NO) pathway and potassium channels in isolated human saphenous veins (SVs) obtained from patients undergoing coronary artery bypass grafting (CABG). GSNO (10-10 M) produced concentration-dependent relaxations in SV rings precontracted with phenylephrine. These relaxations were unaffected by NO synthase inhibition with L-NAME (10 M, 30 min) or NO scavenging with PTIO (10 M, 30 min), but were significantly reduced by the sGC inhibitor, ODQ (10 M, 30 min). Inhibition of ATP-sensitive (glibenclamid; 10 M, 30 min.), high-conductance Ca-activated (charybdotoxin; 10 M, 30 min), small-conductance Ca-activated (apamin; 10 M, 30 min), or voltage-dependent (4-aminopyridine; 10 M, 30 min) potassium channels did not alter the maximum relaxant responses to GSNO. Furthermore, pretreatment with GSNO (10 M, 30 min) significantly attenuated both the contractile response and sensitivity to phenylephrine. Collectively, these findings demonstrate that GSNO exerts acute vasorelaxant and modulatory effects in human SV primarily via cGMP-dependent mechanisms, highlighting its potential as a local therapeutic agent for preventing graft spasm in CABG.
S-亚硝基谷胱甘肽（GSNO）是一种很有前景的亚硝基硫醇，因其具有血管舒张、抗血小板和抗增殖作用而被认为能够调节血管张力。然而，关于其在人体血管中的血管舒张作用的数据仍然有限，其作用机制尚未完全阐明。在本研究中，我们旨在研究GSNO的血管舒张作用及其潜在机制，特别关注从接受冠状动脉旁路移植术（CABG）的患者获取的离体大隐静脉（SV）中的可溶性鸟苷酸环化酶（sGC）/一氧化氮（NO）途径和钾通道。GSNO（10⁻¹⁰ M）使预先用去氧肾上腺素预收缩的SV环产生浓度依赖性舒张。这些舒张不受L-NAME（10 μM，30分钟）抑制一氧化氮合酶或PTIO（10 μM，30分钟）清除NO的影响，但被sGC抑制剂ODQ（10 μM，30分钟）显著减弱。抑制ATP敏感性钾通道（格列本脲；10 μM，30分钟）、高电导钙激活钾通道（蝎毒素；10 μM，30分钟）、小电导钙激活钾通道（蜂毒明肽；10 μM，30分钟）或电压依赖性钾通道（4-氨基吡啶；10 μM，30分钟）均未改变对GSNO的最大舒张反应。此外，用GSNO（10 μM，30分钟）预处理可显著减弱对去氧肾上腺素的收缩反应和敏感性。总体而言，这些发现表明GSNO主要通过cGMP依赖性机制在人体SV中发挥急性血管舒张和调节作用，突出了其作为预防CABG中移植物痉挛的局部治疗剂的潜力。
