Nitrite potentiates the vasodilatory signaling of S-nitrosothiols
Nitrite potentiates the vasodilatory signaling of S-nitrosothiols
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DOI：
10.1016/j.niox.2018.01.011
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发表时间：
2018-05-01
影响因子：
3.9
通讯作者：
Blood, Arlin B.
中科院分区：
文献类型：
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作者：
Liu, Taiming;Zhang, Meijuan;Blood, Arlin B.
亚硝酸盐和 S-亚硝基硫醇 (SNO) 都是一氧化氮 (NO) 代谢的副产物，并被认为通过激活可溶性鸟苷酸环化酶 (sGC) 引起血管舒张。我们之前曾报道过，虽然 SNO 在生理浓度下是有效的血管舒张剂，但亚硝酸盐本身仅在超生理浓度下产生血管舒张作用。在这里，我们测试了亚硝酸盐的亚血管活性浓度会增强 SNO 的血管舒张作用的假设。将离体绵羊动脉多次暴露于 S-亚硝基谷胱甘肽 (GSNO) 会导致对 GSNO 的血管舒张反应快速降低，但不会对 NO 产生反应，表明 sGC 上游的信号传导步骤减弱。动脉暴露于1μM亚硝酸盐增强了幼稚动脉中GSNO的血管舒张作用，并消除了预先暴露的动脉中对GSNO的快速预防反应，表明亚硝酸盐促进了GSNO介导的sGC激活。在完整麻醉的绵羊和大鼠中，抑制NO合酶以降低血浆亚硝酸盐水平会减弱对外源输注GSNO的血管舒张反应，而外源输注低于血管舒张水平的亚硝酸盐可逆转这种效应。这项研究表明，亚硝酸盐通过 sGC 激活上游的机制增强 SNO 介导的血管舒张作用。
Nitrite and S-nitrosothiols (SNOs) are both byproducts of nitric oxide (NO) metabolism and are proposed to cause vasodilation via activation of soluble guanylate cyclase (sGC). We have previously reported that while SNOs are potent vasodilators at physiological concentrations, nitrite itself only produces vasodilation at supraphysiological concentrations. Here, we tested the hypothesis that sub-vasoactive concentrations of nitrite potentiate the vasodilatory effects of SNOs. Multiple exposures of isolated sheep arteries to S-nitroso-glutathione (GSNO) resulted in a tachyphylactic decreased vasodilatory response to GSNO but not to NO, suggesting attenuation of signaling steps upstream from sGC. Exposure of arteries to 1 mu M nitrite potentiated the vasodilatory effects of GSNO in naive arteries and abrogated the tachyphylactic response to GSNO in pre-exposed arteries, suggesting that nitrite facilitates GSNO-mediated activation of sGC. In intact anesthetized sheep and rats, inhibition of NO synthases to decrease plasma nitrite levels attenuated vasodilatory responses to exogenous infusions of GSNO, an effect that was reversed by exogenous infusion of nitrite at sub-vasodilating levels. This study suggests nitrite potentiates SNO-mediated vasodilation via a mechanism that lies upstream from activation of sGC.