Department of Pharmacy, Laboratory of Molecular Pharmacology, University of Patras, Patras, Greece.
Arterioscler Thromb Vasc Biol. 2011 Nov;31(11):2570-6. doi: 10.1161/ATVBAHA.111.229039.
Carbon monoxide (CO) is a weak soluble guanylyl cyclase stimulator, leading to transient increases in cGMP and vasodilation. The aim of the present work was to measure the effect of CO-releasing molecules (CORMs) on the cGMP/nitric oxide (NO) pathway and to evaluate how selected CORMs affect NO-induced vasorelaxation.
Incubation of smooth muscle cells with some but not all of the CORMs caused a minor increase in cGMP levels. Concentration-response curves were bell-shaped, with higher CORMs concentrations producing lower increases in cGMP levels. Although exposure of cells to CORM-2 enhanced cGMP formation, we observed that the compound inhibited NO-stimulated cGMP accumulation in cells and NO-stimulated soluble guanylyl cyclase activity that could be reversed by superoxide anion scavengers. Reactive oxygen species generation from CORMs was confirmed using luminol-induced chemiluminescence and electron spin resonance. Furthermore, we observed that NO is scavenged by CORM-2. When used alone CORM-2 relaxed vessels through a cGMP-mediated pathway but attenuated NO donor-stimulated vasorelaxation.
We conclude that the CORMs examined have context-dependent effects on vessel tone, as they can directly dilate blood vessels, but also block NO-induced vasorelaxation.
一氧化碳（CO）是一种弱可溶性鸟苷酸环化酶刺激剂，导致 cGMP 短暂增加和血管舒张。本研究的目的是测量 CO 释放分子（CORMs）对 cGMP/一氧化氮（NO）途径的影响，并评估选定的 CORMs 如何影响 NO 诱导的血管舒张。
一些但不是所有的 CORMs 孵育平滑肌细胞会导致 cGMP 水平轻微增加。浓度反应曲线呈钟形，较高的 CORMs 浓度会导致 cGMP 水平的增加降低。尽管 CORM-2 暴露于细胞中会增强 cGMP 的形成，但我们观察到该化合物抑制了细胞中 NO 刺激的 cGMP 积累和 NO 刺激的可溶性鸟苷酸环化酶活性，该活性可被超氧阴离子清除剂逆转。使用发光氨诱导的化学发光和电子自旋共振证实了 CORMs 产生的活性氧。此外，我们观察到 CORM-2 会消耗 NO。当单独使用 CORM-2 时，它通过 cGMP 介导的途径使血管松弛，但减弱了 NO 供体刺激的血管舒张。
我们得出结论，所检查的 CORMs 对血管张力具有上下文相关的影响，因为它们可以直接扩张血管，但也可以阻断 NO 诱导的血管舒张。
