Nelli S, McIntosh L, Martin W
Division of Neuroscience and Biomedical Systems, Institute of Biomedical and Life Sciences, West Medical Building, University of Glasgow, G12 8QQ, Scotland, Glasgow, UK.
Eur J Pharmacol. 2001 Feb 2;412(3):281-9. doi: 10.1016/s0014-2999(00)00845-1.
Since copper ions catalyse the oxidation of nitroxyl anion to nitric oxide, we investigated whether this might explain the vasodilator actions of the nitroxyl generator, Angeli's salt, in rat aorta. Parallel studies were conducted with S-nitroso-N-acetyl-D,L-penicillamine (SNAP), since Cu ions catalyse the liberation of nitric oxide from this compound. Copper sulphate enhanced relaxation to Angeli's salt and SNAP but this resulted from reduced destruction of nitric oxide by superoxide rather than from enhanced generation of nitric oxide, since it was mimicked by superoxide dismutase and by the superoxide dismutase mimetic, MnCl2. Results with the selective Cu2+ chelators, neocuproine and bathocuproine disulfonate, and the Cu2+ chelators, EDTA, cuprizone and diethyldithiocarbamate, confirmed an important role for endogenous copper in mediating relaxation to SNAP but suggested only a minor role for Angeli's salt. Relaxation to Angeli's salt was, however, powerfully blocked by proadifen, suggesting an important role for cytochrome P450.
由于铜离子可催化硝酰阴离子氧化为一氧化氮，我们研究了这是否可以解释硝酰发生器安吉利盐在大鼠主动脉中的血管舒张作用。同时对S-亚硝基-N-乙酰-D,L-青霉胺（SNAP）进行了平行研究，因为铜离子可催化该化合物释放一氧化氮。硫酸铜增强了对安吉利盐和SNAP的舒张作用，但这是由于超氧化物对一氧化氮的破坏减少所致，而非一氧化氮生成增加，因为超氧化物歧化酶和超氧化物歧化酶模拟物氯化锰可模拟此效应。选择性铜离子螯合剂新铜试剂和磺酸铜试剂，以及铜离子螯合剂乙二胺四乙酸、铜克酮和二乙基二硫代氨基甲酸盐的实验结果证实，内源性铜在介导对SNAP的舒张作用中起重要作用，但表明其对安吉利盐的作用较小。然而，普罗地芬可强烈阻断对安吉利盐的舒张作用，提示细胞色素P450起重要作用。
