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Nitric Oxide. 2012 Jan 1;26(1):61-73. doi: 10.1016/j.niox.2011.12.002. Epub 2011 Dec 14.

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

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  • 1Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organisation, Timarpur, Delhi, India.

Abstract

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.

PMID:
22197744
DOI:
10.1016/j.niox.2011.12.002
[PubMed - indexed for MEDLINE]
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