Abstract:
:Inorganic nitrite (NO(2)(-)) is emerging as a regulator of physiological functions and tissue responses to ischemia, whereas the more stable nitrate anion (NO(3)(-)) is generally considered to be biologically inert. Bacteria express nitrate reductases that produce nitrite, but mammals lack these specific enzymes. Here we report on nitrate reductase activity in rodent and human tissues that results in formation of nitrite and nitric oxide (NO) and is attenuated by the xanthine oxidoreductase inhibitor allopurinol. Nitrate administration to normoxic rats resulted in elevated levels of circulating nitrite that were again attenuated by allopurinol. Similar effects of nitrate were seen in endothelial NO synthase-deficient and germ-free mice, thereby excluding vascular NO synthase activation and bacteria as the source of nitrite. Nitrate pretreatment attenuated the increase in systemic blood pressure caused by NO synthase inhibition and enhanced blood flow during post-ischemic reperfusion. Our findings suggest a role for mammalian nitrate reduction in regulation of nitrite and NO homeostasis.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Jansson EA,Huang L,Malkey R,Govoni M,Nihlén C,Olsson A,Stensdotter M,Petersson J,Holm L,Weitzberg E,Lundberg JOdoi
10.1038/nchembio.92subject
Has Abstractpub_date
2008-07-01 00:00:00pages
411-7issue
7eissn
1552-4450issn
1552-4469pii
nchembio.92journal_volume
4pub_type
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