Article abstract
Nature Chemical Biology 4, 411 - 417 (2008)
Published online: 30 May 2008 | doi:10.1038/nchembio.92
A mammalian functional nitrate reductase that regulates nitrite and nitric oxide homeostasis
Emmelie Å Jansson1, Liyue Huang1, Ronny Malkey1, Mirco Govoni1, Carina Nihlén1, Annika Olsson1, Margareta Stensdotter1, Joel Petersson2, Lena Holm2, Eddie Weitzberg3 & Jon O Lundberg1
Abstract
Inorganic nitrite (NO2-) is emerging as a regulator of physiological functions and tissue responses to ischemia, whereas the more stable nitrate anion (NO3-) 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.
- Department of Physiology and Pharmacology, Karolinska Institutet, Nanna Svartz väg 2, SE-171 77 Stockholm, Sweden.
- Department of Physiology and Pharmacology, Division of Anesthesiology and Intensive Care, Karolinska Institutet, Nanna Svartz väg 2, SE-171 77 Stockholm, Sweden.
- Department of Medical Cell Biology, Box 571, Uppsala University, SE-751 23 Uppsala, Sweden.
Correspondence to: Jon O Lundberg1 e-mail: jon.lundberg@ki.se
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