Dietary nitrite attenuates oxidative stress and activates antioxidant genes in rat heart during hypobaric hypoxia

作者：Singh Manjulata; Arya Aditya; Kumar Rajesh; Bhargava Kalpana^*; Sethy Niroj Kumar

来源：Nitric Oxide-Biology and Chemistry, 2012, 26(1): 61-73.

DOI：10.1016/j.niox.2011.12.002

• Nitrite
• Heart
• Nitric oxide
• Hypoxia
• Oxidative stress

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-1 alpha 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.

• 出版日期2012-1-1