Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organisation, Timarpur, Delhi, India.
Nitric Oxide. 2012 Jan 1;26(1):61-73. doi: 10.1016/j.niox.2011.12.002. Epub 2011 Dec 14.
The nitrite anion represents the circulatory and tissue storage form of nitric oxide (NO) and a signaling molecule, capable of conferring cardioprotection and many other health benefits. However, molecular mechanisms for observed cardioprotective properties of nitrite remain largely unknown. We have evaluated the NO-like bioactivity and cardioprotective efficacies of sodium nitrite supplemented in drinking water in rats exposed to short-term chronic hypobaric hypoxia. We observed that, nitrite significantly attenuates hypoxia-induced oxidative stress, modulates HIF-1α stability and promotes NO-cGMP signaling in hypoxic heart. To elucidate potential downstream targets of nitrite during hypoxia, we performed a microarray analysis of nitrite supplemented hypoxic hearts and compared with both hypoxic and nitrite supplemented normoxic hearts respectively. The analysis revealed a significant increase in the expression of many antioxidant genes, transcription factors and cardioprotective signaling pathways which was subsequently confirmed by qRT-PCR and Western blotting. Conversely, hypoxia exposure increased oxidative stress, activated inflammatory cytokines, downregulated ion channels and altered expression of both pro- and anti-oxidant genes. Our results illustrate the physiological function of nitrite as an eNOS-independent source of NO in heart profoundly modulating the oxidative status and cardiac transcriptome during hypoxia.
亚硝酸盐阴离子代表一氧化氮（NO）的循环和组织储存形式，也是一种信号分子，能够提供心脏保护和许多其他健康益处。然而，亚硝酸盐观察到的心脏保护特性的分子机制在很大程度上仍然未知。我们评估了补充到饮用水中的亚硝酸钠在短期慢性低压缺氧暴露的大鼠中的类似一氧化氮的生物活性和心脏保护功效。我们观察到，亚硝酸盐显著减轻缺氧诱导的氧化应激，调节 HIF-1α 的稳定性，并促进缺氧心脏中的 NO-cGMP 信号。为了阐明缺氧期间亚硝酸盐的潜在下游靶标，我们对补充亚硝酸盐的缺氧心脏进行了微阵列分析，并分别与缺氧和补充亚硝酸盐的常氧心脏进行了比较。分析显示，许多抗氧化基因、转录因子和心脏保护信号通路的表达显著增加，随后通过 qRT-PCR 和 Western blot 进行了验证。相反，缺氧暴露增加了氧化应激，激活了炎症细胞因子，下调了离子通道，并改变了氧化和抗氧化基因的表达。我们的结果说明了亚硝酸盐作为心脏中 eNOS 独立的一氧化氮来源的生理功能，在缺氧期间显著调节氧化状态和心脏转录组。
