Selective blockade of endothelium-dependent and glyceryl trinitrate-induced relaxation by hemoglobin and by methylene blue in the rabbit aorta.
Selective blockade of endothelium-dependent and glyceryl trinitrate-induced relaxation by hemoglobin and by methylene blue in the rabbit aorta.
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发表时间：
1985-03
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通讯作者：
W. Martin;G. Villani;D. Jothianandan;R. Furchgott
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作者：
W. Martin;G. Villani;D. Jothianandan;R. Furchgott
在兔主动脉环中，1 μ M的血红蛋白减少，10 μ M的血红蛋白消除乙酰胆碱或A23187诱导的内皮依赖性舒张。同样，亚甲蓝在10 μ M减少和在50 μ M废除由乙酰胆碱和A23187诱导的松弛。此外，血红蛋白（1-10 μ M）和亚甲基蓝（10-50 μ M）均诱导三硝酸甘油酯产生的内皮非依赖性舒张的剂量依赖性抑制，但对异丙肾上腺素产生的舒张均无任何影响。血红蛋白和亚甲蓝的抑制作用可能是由于鸟苷酸环化酶的阻断，因为伴随乙酰胆碱，A23187或甘油三硝酸酯诱导的松弛的环GMP含量的上升被取消。异丙肾上腺素诱导的舒张发生在环GMP含量没有变化。因此，血红蛋白和亚甲蓝似乎选择性地抑制由增加环GMP水平的药剂诱导的血管舒张。血红蛋白和亚甲蓝增加主动脉环的张力，特别是当存在内皮细胞时，表明内皮源性舒张因子（EDRF）可能在低浓度下自发释放。血红蛋白抑制内皮依赖性和甘油三硝酸酯诱导的松弛结合EDRF和一氧化氮的可能性，分别进行了讨论，连同建议，亚甲基蓝可能产生的影响，通过氧化鸟苷酸环化酶的一个组成部分，可能是一个亚铁血红素基团连接到酶分子。此外，亚甲蓝可能与EDRF直接相互作用。
Hemoglobin at 1 microM reduced and at 10 microM abolished the endothelium-dependent relaxation induced by acetylcholine or by A23187 in rabbit aortic rings. Similarly, methylene blue at 10 microM reduced and at 50 microM abolished relaxation induced by acetylcholine and by A23187. Furthermore, hemoglobin (1-10 microM) and methylene blue (10-50 microM) each induced a dose-dependent inhibition of the endothelium-independent relaxation produced by glyceryl trinitrate, but neither had any effect on the relaxation produced by isoproterenol. The inhibitory effects of hemoglobin and methylene blue may be due to blockade of guanylate cyclase, as the rises in cyclic GMP content which accompany relaxation induced by acetylcholine, A23187 or glyceryl trinitrate were abolished. Isoproterenol-induced relaxation took place with no change in cyclic GMP content. Hemoglobin and methylene blue appear therefore to inhibit selectively vaso-relaxation induced by agents which increase cyclic GMP levels. Hemoglobin and methylene blue augment tone in aortic rings, particularly when endothelial cells are present, suggesting that the endothelium-derived relaxing factor (EDRF) might be released spontaneously in low concentrations. The possibility that hemoglobin inhibits endothelium-dependent and glyceryl trinitrate-induced relaxation by binding EDRF and nitric oxide, respectively, is discussed together with the proposal that methylene blue might produce its effects by oxidizing a component of guanylate cyclase, possibly a ferrous heme group linked to the enzyme molecule. Methylene blue might, in addition, interact directly with EDRF.