MODULATION OF THE PHARMACOLOGICAL ACTIONS OF NITROVASODILATORS BY METHYLENE-BLUE AND PYOCYANIN
MODULATION OF THE PHARMACOLOGICAL ACTIONS OF NITROVASODILATORS BY METHYLENE-BLUE AND PYOCYANIN
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DOI：
10.1111/j.1476-5381.1992.tb14422.x
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发表时间：
1992-08-01
影响因子：
7.3
通讯作者：
VANE, JR
中科院分区：
文献类型：
--
作者：
GRYGLEWSKI, RJ;ZEMBOWICZ, A;VANE, JR
1在灌流预收缩的兔主动脉条中，1-10 μ M浓度的亚甲蓝（MeB）或绿脓菌素（Pyo，1-羟基-5-甲基吩嗪甜菜碱）抑制内皮源性舒张因子（EDRF）、硝酸甘油酯（GTN）、S-亚硝基-N-乙酰青霉胺（SNAP）或3-吗啉代-悉尼酮亚胺（SIN-1）诱导的舒张。然而，硝普钠（NnNP）或亚硝酸钠（NaNO 2）的血管舒张作用被MeB或Pyo增强。氧合血红蛋白（HbO 2，1 μ M）抑制EDRF和所有的硝基血管扩张剂的活动研究。除非用NaNP（0.05-10 μ M）预处理，否则Pyo不会使血管制剂松弛。2在浸泡的预收缩兔主动脉环中，Pyo（10 μ M）使NaNP（0.01-10 μ M）的累积浓度-反应曲线向左移动。鸟苷-3 '的增加：5'-环状单磷酸酯主动脉组织环磷酸鸟苷含量也增加。3. NaNP的血管舒张作用在pH 5-8和37 ℃下，SNAP（30 μ M）的溶液在2.5小时内保持不变，（30 μ M）在60分钟内逐渐失去其生物活性。（150 μ M）或表雄酮（150 μ M），而血管舒张效力NaNP（30 μ M）与MeB或Pyo.4孵育时加倍。在人富血小板血浆中，MeB或Pyo（0.3-3.0 μ M）揭示了亚阈值浓度的NaNP（4-8 μ M）的抗聚集作用。这被HbO 2（10 μ M）消除。与NaNP相反，SNAP（2-20 μ M）的抗聚集作用被MeB（10 μ M）、Pyo（10 μ M）或HbO 2（10 μ M）拮抗。5我们得出结论，MeB或Pyo与HbO 2在与硝基血管扩张剂的相互作用模式上不同。HbO 2清除从所有类型的硝基血管扩张剂释放的一氧化氮。MeB和Pyo对有机硝基血管扩张剂（例如SNAP，SIN-1）发挥类似的作用。然而，无机硝基血管扩张剂（例如NaNP或NaNO 2）的药理作用被MeB和Pyo增强，这是由于促进了来自无机硝基血管扩张剂的一氧化氮的细胞内释放。
1 In superfused precontracted strips of rabbit aorta, methylene blue (MeB) or pyocyanin (Pyo, 1-hydroxy-5-methyl phenazinum betaine) at concentrations of 1-10-mu-M inhibited relaxations induced by endothelium-derived relaxing factor (EDRF), glyceryl trinitrate (GTN), S-nitroso-N-acetyl-penicillamine (SNAP) or 3-morpholino-sydnonimine (SIN-1). However, the vasorelaxant actions of sodium nitroprusside (NnNP) or sodium nitrite (NaNO2) were enhanced by MeB or Pyo. Oxyhaemoglobin (HbO2, 1-mu-M) inhibited the activities of EDRF and all of the nitrovasodilators studied. Vascular preparations were not relaxed by Pyo unless pretreated with NaNP (0.05-10-mu-M).2 In bathed, precontracted rings of rabbit aorta, Pyo (10-mu-M) produced a shift to the left of the cumulative concentration-response curve for NaNP (0.01-10-mu-M). The rise in guanosine-3':5'-cyclic monophosphate (cyclic GMP) content of aortic tissue was also enhanced.3 The vasorelaxant potency of NaNP (30-mu-M) at pH 5-8 and at 37-degrees-C remained unchanged over 2.5 h while a solution of SNAP (30-mu-M) progressively lost its biological activity over 60 min. The in vitro degradation of the biological activity of SNAP was accelerated by MeB (150-mu-M) or Pyo (150-mu-M), whereas the vasorelaxant potency NaNP (30-mu-M) was doubled when incubated with MeB or Pyo.4 In human platelet-rich plasma, MeB or Pyo (0.3-3.0-mu-M) uncovered an anti-aggregatory action of subthreshold concentrations of NaNP (4-8-mu-M). This was abrogated by HbO2 (10-mu-M). In contrast to NaNP the anti-aggregatory effect of SNAP (2-20-mu-M) was antagonized by MeB (10-mu-M), Pyo (10-mu-M) or HbO2 (10-mu-M).5 We conclude that MeB or Pyo differ from HbO2 in their mode of interaction with nitrovasodilators. HbO2 scavenges nitric oxide that is released from all types of nitrovasodilators. MeB and Pyo exert a similar action towards organic nitrovasodilators (e.g. SNAP, SIN-1). However, the pharmacological actions of inorganic nitrovasodilators (e.g. NaNP or NaNO2) are potentiated by MeB and Pyo owing to facilitation of the intracellular release of nitric oxide from the inorganic nitrovasodilators.