Department of Pharmacology, Ghent University, Ghent, Belgium.
Eur J Pharmacol. 2012 Jan 15;674(2-3):370-7. doi: 10.1016/j.ejphar.2011.11.004. Epub 2011 Nov 12.
Carbon monoxide (CO) may play an important physiological role in regulation of the vascular tone. CO-releasing molecule (CORM-2) is frequently used as a CO-donor to evaluate (patho)physiological properties of CO and its potential therapeutic applications. The aim of this study was to examine the molecular mechanisms underlying the vasodilatory properties of CORM-2 as this has not yet been extensively explored. Isometric tension recordings were performed using mice and rat isolated aortic ring segments as well as mice femoral artery ring segments. Responses to CO (10 μmol/l-300 μmol/l) and CORM-2 (30 μmol/l-600 μmol/l) were evaluated in the presence/absence of activators/inhibitors of different molecular pathways. CO was unable to relax mice blood vessels, whereas it induced concentration-dependent relaxations in rat aorta. The response to CO was inhibited by both the soluble guanylyl cyclase (sGC) inhibitor ODQ (10 μmol/l) and potassium (K(+)) channel blocker tetraethyl-ammonium chloride (3 mmol/l). CORM-2 relaxed both mice and rat isolated blood vessels in a concentration-dependent manner, however this response was only partially blocked by ODQ and tetraethyl-ammonium chloride. Interestingly, 4-aminopyridine (3 mmol/l) inhibited the CORM-2 induced vasodilatation whereas iberiotoxin (100 nmol/l) had no influence. The molecular mechanisms underlying CORM-2 induced relaxation differ from those of CO-induced relaxation. While CO relaxes vessels through activation of sGC and/or calcium-activated K(+)-channels, CORM-2 exerts its vasodilatory properties only partially through sGC or K(+)-channels activation. CORM-2 induced vasodilatation seems to involve voltage-dependent rather than calcium-activated K(+)-channels.
一氧化碳（CO）可能在血管张力调节中发挥重要的生理作用。一氧化碳释放分子（CORM-2）常被用作 CO 供体，以评估 CO 的（病理）生理学特性及其潜在的治疗应用。本研究旨在探讨 CORM-2 血管舒张特性的分子机制，因为这尚未得到广泛探讨。使用小鼠和大鼠离体主动脉环段以及小鼠股动脉环段进行等长张力记录。在不同分子途径的激活剂/抑制剂存在/不存在的情况下，评估 CO（10 μmol/l-300 μmol/l）和 CORM-2（30 μmol/l-600 μmol/l）的反应。CO 不能使小鼠血管舒张，而在大鼠主动脉中诱导浓度依赖性舒张。CO 的反应被可溶性鸟苷酸环化酶（sGC）抑制剂 ODQ（10 μmol/l）和钾（K+）通道阻滞剂四乙铵氯化物（3 mmol/l）抑制。CORM-2 以浓度依赖性方式使小鼠和大鼠离体血管舒张，但该反应仅部分被 ODQ 和四乙铵氯化物阻断。有趣的是，4-氨基吡啶（3 mmol/l）抑制 CORM-2 诱导的血管舒张，而 Iberiotoxin（100 nmol/l）没有影响。CORM-2 诱导的舒张的分子机制与 CO 诱导的舒张不同。虽然 CO 通过激活 sGC 和/或钙激活的 K+通道使血管舒张，但 CORM-2 仅部分通过 sGC 或 K+通道激活发挥其血管舒张特性。CORM-2 诱导的血管舒张似乎涉及电压依赖性而非钙激活的 K+通道。
