title: Role of blood and vascular smooth muscle in the vasoactivity of nitrite.
abstract: Recent evidence from humans and rats indicates that nitrite is a vasodilator under hypoxic conditions by reacting with metal-containing proteins to produce nitric oxide (NO). We tested the hypothesis that near-physiological concentrations of nitrite would produce vasodilation in a hypoxia- and concentration-dependent manner in the hind limb of sheep. Anesthetized sheep were instrumented to measure arterial blood pressure and femoral blood flows continuously in both hind limbs. Nitrite was infused into one femoral artery to raise the nitrite concentration in the femoral vein by 10 to 15-fold while the sheep breathed 50%, 14% or 12% oxygen in inspired air. In contrast to reports in humans and rats, the nitrite infusion had no measurable effect on mean femoral blood flows or vascular conductances, regardless of inspired O2 levels. In vitro experiments showed no significant difference in the release of NO from nitrite in sheep and human red blood cells. Further experiments demonstrated nitrite is converted to NO in rat artery homogenates faster than sheep arteries, and that this source of NO production is attenuated in the presence of a heme oxidizer. Finally, western blots indicate that concentrations of the heme-containing protein cytoglobin, but not myoglobin, are markedly lower in sheep arteries compared with rats. Overall, the results demonstrate that nitrite is not a physiological vasodilator in sheep. This is likely due to a lack of conversion of nitrite to NO within the vascular smooth muscle, perhaps due to deficient amounts of the heme-containing protein cytoglobin.
authors.affiliation: Department of Pediatrics, Division of Neonatology, Loma Linda University School of Medicine, Loma Linda, California;
authors.forename: Taiming
authors.initials: T
authors.lastname: Liu
authors.affiliation: Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, California; and.
authors.forename: Hobe J
authors.initials: HJ
authors.lastname: Schroeder
authors.affiliation: Department of Pediatrics, Division of Neonatology, Loma Linda University School of Medicine, Loma Linda, California;
authors.forename: Lisa
authors.initials: L
authors.lastname: Barcelo
authors.affiliation: Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, California; and.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Bragg
authors.affiliation: Department of Respiratory Care, Loma Linda University School of Medicine, Loma Linda, California.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Terry
authors.affiliation: Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, California; and.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Wilson
authors.affiliation: Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, California; and.
authors.forename: Gordon G
authors.initials: GG
authors.lastname: Power
authors.affiliation: Department of Pediatrics, Division of Neonatology, Loma Linda University School of Medicine, Loma Linda, California; Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, California; and ablood@llu.edu.
authors.forename: Arlin B
authors.initials: AB
authors.lastname: Blood
mesh_terms: D000818:Animals; D000078842:Cytoglobin; D005260:Female; D005263:Femoral Artery / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D005914:Globins / Q000378:metabolism; D006614:Hindlimb / Q000098:blood supply; D000860:Hypoxia / Q000097:blood / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism; D009573:Nitrites / Q000097:blood* / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D051381:Rats; D012039:Regional Blood Flow; D012756:Sheep; D014664:Vasodilation
chemical_list: C000627265:CYGB protein, human; C000627268:Cygb protein, rat; D000078842:Cytoglobin; D009573:Nitrites; D009569:Nitric Oxide; D005914:Globins; D010100:Oxygen
keywords: femoral artery; hypoxic vasodilation; nitric oxide; nitrite; sheep
references.citation: J Appl Physiol (1985). 2011 Jun;110(6):1582-91
references.pmid: 21454745
references.citation: Nitric Oxide. 2009 Sep;21(2):92-103
references.pmid: 19602444
references.citation: Biochem Biophys Res Commun. 2010 May 21;396(1):39-45
references.pmid: 20494108
references.citation: Nat Chem Biol. 2005 Oct;1(5):290-7
references.pmid: 16408059
references.citation: Proc Natl Acad Sci U S A. 2007 Nov 6;104(45):17593-8
references.pmid: 17971439
references.citation: Nat Med. 2003 Dec;9(12):1498-505
references.pmid: 14595407
references.citation: Am J Physiol Heart Circ Physiol. 2006 Nov;291(5):H2026-35
references.pmid: 16798825
references.citation: J Biol Chem. 2012 Oct 19;287(43):36623-33
references.pmid: 22896706
references.citation: Free Radic Biol Med. 2003 Oct 1;35(7):790-6
references.pmid: 14583343
references.citation: Med Sci Sports Exerc. 2014 Jan;46(1):143-50
references.pmid: 23846159
references.citation: FEBS J. 2013 Aug;280(15):3621-31
references.pmid: 23710929
references.citation: J Neurosci Methods. 2008 Jul 30;172(2):250-4
references.pmid: 18571732
references.citation: Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):336-41
references.pmid: 12502793
references.citation: Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12814-9
references.pmid: 11606734
references.citation: Circ Res. 2007 Jun 22;100(12):1749-54
references.pmid: 17495223
references.citation: Cardiovasc Res. 2011 Feb 15;89(3):560-5
references.pmid: 20889759
references.citation: Blood. 2005 Jul 15;106(2):734-9
references.pmid: 15774613
references.citation: J Appl Physiol (1985). 2013 Aug 1;115(3):325-36
references.pmid: 23640589
references.citation: Br J Haematol. 2008 Sep;142(6):971-8
references.pmid: 18671702
references.citation: Nitric Oxide. 2007 Jun;16(4):448-56
references.pmid: 17517526
references.citation: Biochim Biophys Acta. 1999 May 5;1411(2-3):250-62
references.pmid: 10320661
references.citation: Am J Physiol Heart Circ Physiol. 2009 Feb;296(2):H237-46
references.pmid: 19028797
references.citation: Free Radic Biol Med. 2006 Aug 15;41(4):541-8
references.pmid: 16863986
references.citation: J Clin Invest. 2005 Aug;115(8):2099-107
references.pmid: 16041407
references.citation: Circulation. 2012 Jul 17;126(3):325-34
references.pmid: 22685116
references.citation: Blood. 2006 Jan 15;107(2):566-74
references.pmid: 16195332
references.citation: Am J Physiol Heart Circ Physiol. 2008 Aug;295(2):H499-508
references.pmid: 18539756
references.citation: Proc Natl Acad Sci U S A. 2004 Aug 3;101(31):11477-82
references.pmid: 15258287
references.citation: Circulation. 2008 Feb 5;117(5):670-7
references.pmid: 18212289
references.citation: Proc Natl Acad Sci U S A. 2006 May 30;103(22):8366-71
references.pmid: 16717191
references.citation: Am J Physiol Heart Circ Physiol. 2007 Sep;293(3):H1508-17
references.pmid: 17513487
references.citation: J Physiol. 2014 Apr 15;592(8):1785-94
references.pmid: 24535441
references.citation: Nat Chem Biol. 2007 Dec;3(12):785-94
references.pmid: 17982448
references.citation: Am J Physiol Heart Circ Physiol. 2007 Jun;292(6):H3072-8
references.pmid: 17307993
references.citation: Circulation. 2007 Oct 16;116(16):1821-31
references.pmid: 17893272
references.citation: Cell Mol Life Sci. 2007 Jan;64(1):96-103
references.pmid: 17160351
references.citation: J Biol Chem. 2005 Sep 2;280(35):31126-31
references.pmid: 15837788
references.citation: Cardiovasc Res. 2007 Jul 15;75(2):327-38
references.pmid: 17568573