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

• DOI: 10.1016/j.niox.2011.12.002
• Publication Date: 2011-12-15T00:06:36Z
• Authors: Manjulata Singh; Aditya Arya; Rajesh Kumar; Kalpana Bhargava; Niroj Kumar Sethy
• Keywords: Male; 0301 basic medicine; Nitric Oxide Synthase Type III; Myocardium; Heart; Hypoxia-Inducible Factor 1, alpha Subunit; Nitric Oxide; Antioxidants; Rats; 3. Good health; Rats, Sprague-Dawley; Oxidative Stress; 03 medical and health sciences; Gene Expression Regulation; Dietary Supplements; Animals; Hypoxia; Transcriptome; Cyclic GMP; Nitrites; Signal Transduction

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.