Vanin Anatoly F, Mokh Vladimir P, Serezhenkov Vladimir A, Chazov Evgeny I
Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow, Russia.
Nitric Oxide. 2007 May;16(3):322-30. doi: 10.1016/j.niox.2006.12.003. Epub 2006 Dec 22.
Vasorelaxant activity of new stable powder preparations of dinitrosyl iron complexes (DNIC) with thiol-containing ligands was investigated on rat abdominal aorta rings. The preparations preserve their physicochemical characteristics (EPR and optical absorption) if stored for a long time in dry air (at least half-year). Three preparations of DNIC were tested: diamagnetic dimeric DNIC with glutathione (DNIC-GS 1:2) or cysteine (DNIC-cys 1:2) and paramagnetic monomeric DNIC with cysteine (DNIC-cys 1:20). Being dissolved in physiological solution the preparations induced relaxation of vessel similarly to that by earlier described non-stable DNICs which should be stored in liquid nitrogen. The amplitudes and kinetic characteristics of the relaxation were dependent on the incorporated thiolate ligands. Rapid transient relaxation followed by significant tone recovery to stationary level (plateau) was observed for DNIC-cys 1:2. DNIC-cys 1:20 also induced initial rapid relaxation followed by incomplete tone recovery. DNIC-GS 1:2 induced slow developing and long lasting relaxation. NO scavenger, hydroxocobalamin (2x10(-5)M) eliminated the rapid transitory relaxation induced by DNIC-cys 1:20 and did not influence significantly on the plateau level. SOD increased duration of the DNIC-cys 1:2 and DNIC-cys 1:20 induced relaxation. The addition of 5x10(-5)M DNIC-cys 1:2 or DNIC-cys 1:20 induced long lasting vasorelaxation within 20min and more. However the EPR measurements demonstrated full rapid disappearance (within 1-2min) of both type of DNIC-cys in Krebs medium bubbled with carbogen gas. This was not the case for DNIC-GS 1:2. We suggested that the long lasting vasorelaxation observed during the addition of DNICs-cys was induced by S-nitrosocysteine derived from DNICs-cys and stabilized by EDTA in Krebs medium. The suggestion is in line with the fact that strong ferrous chelator bathophenantroline disulfonate (BPDS) which is capable of rapid degradation of DNICs did not abrogate the vasorelaxtion induced by DNIC addition.
研究了含硫醇配体的二亚硝基铁配合物（DNIC）新型稳定粉末制剂对大鼠腹主动脉环的血管舒张活性。如果在干燥空气中长时间储存（至少半年），这些制剂能保持其物理化学特性（电子顺磁共振和光吸收）。测试了三种DNIC制剂：与谷胱甘肽（DNIC-GS 1:2）或半胱氨酸（DNIC-cys 1:2）形成的抗磁性二聚体DNIC，以及与半胱氨酸（DNIC-cys 1:20）形成的顺磁性单体DNIC。这些制剂溶解于生理溶液后，与先前描述的需储存在液氮中的不稳定DNIC一样，能诱导血管舒张。舒张的幅度和动力学特征取决于所含的硫醇盐配体。观察到DNIC-cys 1:2能引起快速的短暂舒张，随后张力显著恢复至稳定水平（平台期）。DNIC-cys 1:20也能诱导初始的快速舒张，但张力恢复不完全。DNIC-GS 1:2诱导的舒张发展缓慢且持续时间长。一氧化氮清除剂羟基钴胺素（2×10⁻⁵M）消除了DNIC-cys 1:20诱导的快速短暂舒张，且对平台期水平无显著影响。超氧化物歧化酶增加了DNIC-cys 1:2和DNIC-cys 1:20诱导的舒张持续时间。加入5×10⁻⁵M的DNIC-cys 1:2或DNIC-cys 1:20能在20分钟及更长时间内诱导持久的血管舒张。然而，电子顺磁共振测量表明，在通有卡波金气体的Krebs培养基中，两种类型的DNIC-cys均在1 - 2分钟内迅速完全消失。DNIC-GS 1:2的情况并非如此。我们认为，添加DNIC-cys期间观察到的持久血管舒张是由DNIC-cys衍生的S-亚硝基半胱氨酸诱导的，并在Krebs培养基中由乙二胺四乙酸稳定。这一推测与以下事实相符：能够快速降解DNIC的强亚铁螯合剂4,7-二苯基-1,10-菲咯啉二磺酸（BPDS）不会消除添加DNIC诱导的血管舒张。
