title: The roles of tissue nitrate reductase activity and myoglobin in securing nitric oxide availability in deeply hypoxic crucian carp.
abstract: In mammals, treatment with low doses of nitrite has a cytoprotective effect in ischemia/reperfusion events, as a result of nitric oxide formation and S-nitrosation of proteins. Interestingly, anoxia-tolerant lower vertebrates possess an intrinsic ability to increase intracellular nitrite concentration during anoxia in tissues with high myoglobin and mitochondria content, such as the heart. Here, we tested the hypothesis that red and white skeletal muscles develop different nitrite levels in crucian carp exposed to deep hypoxia and assessed whether this correlates with myoglobin concentration. We also tested whether liver, muscle and heart tissue possess nitrate reductase activity that supplies nitrite to the tissues during severe hypoxia. Crucian carp exposed to deep hypoxia (1<PO2<3 mmHg) for 1 day increased nitrite in red musculature to more than double the value in normoxic fish, while nitrite was unchanged in white musculature. There was a highly significant positive correlation between tissue concentrations of nitrite and nitros(yl)ated compounds. Myoglobin levels were 7 times higher in red than in white musculature, but there was no clear correlation between nitrite and myoglobin levels. Finally, we found a low but significant nitrate reductase activity in liver and white muscle, but not in cardiomyocytes. Nitrate reduction was inhibited by allopurinol, showing that it was partly catalyzed by xanthine oxidoreductase.
authors.affiliation: Department of Biology, University of Southern Denmark, Odense M DK-5230, Denmark.
authors.forename: Marie N
authors.initials: MN
authors.lastname: Hansen
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institute, Stockholm SE-17177, Sweden.
authors.forename: Jon O
authors.initials: JO
authors.lastname: Lundberg
authors.affiliation: Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Arcavacata di Rende (CS), Italy.|Zoophysiology, Department of Bioscience, Aarhus University, Aarhus C DK-8000, Denmark.
authors.forename: Mariacristina
authors.initials: M
authors.lastname: Filice
authors.affiliation: Zoophysiology, Department of Bioscience, Aarhus University, Aarhus C DK-8000, Denmark.
authors.forename: Angela
authors.initials: A
authors.lastname: Fago
authors.affiliation: Department of Biology, University of Southern Denmark, Odense M DK-5230, Denmark.
authors.forename: Nanna M G
authors.initials: NM
authors.lastname: Christensen
authors.affiliation: Department of Biology, University of Southern Denmark, Odense M DK-5230, Denmark fbj@biology.sdu.dk.
authors.forename: Frank B
authors.identifier: 0000-0001-6148-6663
authors.initials: FB
authors.lastname: Jensen
mesh_terms: D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D002347:Carps / Q000097:blood / Q000378:metabolism*; D005260:Female; D000860:Hypoxia / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D055442:Metabolome / Q000187:drug effects; D009132:Muscles / Q000187:drug effects / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D009211:Myoglobin / Q000378:metabolism*; D009565:Nitrate Reductases / Q000378:metabolism*; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D009928:Organ Specificity / Q000187:drug effects
chemical_list: D009211:Myoglobin; D009573:Nitrites; D009569:Nitric Oxide; D000493:Allopurinol; D009565:Nitrate Reductases
keywords: Ethanol; Hypoxia; Nitrate reduction; Nitric oxide; Nitrite; Red muscle