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Int J Sports Med 2000; 21(2): 83-89
DOI: 10.1055/s-2000-8874
Physiology and Biochemistry
Georg Thieme Verlag Stuttgart ·New York

Nitric Oxide Biomarkers Increase During Exercise-Induced Vasodilation in the Forearm

 M. D. Brown1, 5 ,  M. Srinivasan1 ,  R. V. Hogikyan1, 4 ,  D. R. Dengel1, 4 ,  S. G. Glickman3 ,  A. Galecki2, 4 ,  M. A. Supiano1, 2, 4
  • 1 Department of Internal Medicine, Division of Geriatric Medicine
  • 2 Institute of Gerontology
  • 3 Division of Kinesiology, University of Michigan
  • 4 GRECC, Ann Arbor Veterans Affairs Medical Center, Ann Arbor, Michigan
  • 5 Department of Kinesiology, University of Maryland, College Park, Maryland, USA
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Publication History

Publication Date:
31 December 2000 (online)

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The purpose of the study was to determine if exercise-induced vasodilation was associated with an increase in forearm plasma levels of nitric oxide (NO) biomarkers (NO2 - + NO3 - and L-citrulline). Twelve healthy subjects (27 ± 6 yrs) performed incremental rhythmic forearm exercise with the nondominant hand for 6 min each at 15, 30 and 45 % of maximal voluntary contraction (MVC). Forearm blood flow (FBF) was determined in the exercise arm using venous occlusion plethysmography. Blood samples were obtained from the antecubital vein of the exercise and nonexercise arms for the measurement of NO biomarkers. In the exercise arm, FBF increased by a mean of 150 %, 335 % and 585 % above baseline at 15, 30 and 45 % of MVC, respectively. (ANOVA, P = 0.0001). Venous plasma NO2 - + NO3 - levels increased from 24 ± 4 µmol/L at baseline, to 29 ± 5, 32 ± 4 and 35 ± 4 µmol/L (ANOVA, P = 0.0001). Venous plasma L-citrulline levels increased from 31 ± 5 µmol/L at baseline to 58 ± 10, 87 ± 7 and 141 ±15 µmol/L (ANOVA, P = 0.0001). There was a linear relationship between FBF and venous plasma NO2 - + NO3 - (slope =0.38 ± 0.10, P = 0.0007) and between L-citrulline, (slope =5.1 ± 1.3, P = 0.0004). Venous plasma levels of NO2 - + NO3 - and L-citrulline in the nonexercise arm were unchanged. These results demonstrate that exercise-induced vasodilation in the forearm is associated with forearm plasma levels of NO2 - + NO3 - and L-citrulline, in vivo markers of NO production.

Key words:

Blood flow - endothelium-derived relaxing factors - exercise - skeletal muscle

References

  • 1 Akiyama K, Suzuki H, Bing R J. Oxidation products of nitric oxide, NO2 and NO3, in plasma after experimental myocardial infarction.  J Mol Cell Cardiol. 1997;  29 1-9
    CrossrefPubMedGoogle Scholar
  • 2 Avogaro A, Piarulli F, Valero P, Miola M, Calveri M, Pavan P, Vicini P, Cobelli C, Tiengo A, Calo L, Del Prato S. Forearm nitric oxide balance, vascular relaxation, and glucose metabolism in NIDDM patients.  Diabetes. 1997;  46 1040-1046
    PubMedGoogle Scholar
  • 3 Balon T W, Nadler J L. Nitric oxide release is present from incubated skeletal muscle preparations.  J Appl Physiol. 1994;  77 2519-2521
    CrossrefPubMedGoogle Scholar
  • 4 Bernstein R D, Ochoa F Y, Xu X, Forfia P, Shen W, Thompson C I, Hintz T H. Function and production of nitric oxide in the coronary circulation of the conscious dog during exercise.  Circ Res. 1996;  79 840-848
    PubMedGoogle Scholar
  • 5 Bode-Boger S M, Boger R H, Creutzig A, Tsikas D, Gutzki F M, Alexander K, Frolich J C. L-Arginine infusion decreases peripheral arterial resistance and inhibits platelet aggregation in healthy subjects.  Clin Sci. 1994;  87 303-310
    PubMedGoogle Scholar
  • 6 Bode-Boger S M, Boger R H, Schroder E P, Frohlich J C. Exercise increases systemic nitric oxide production in men.  J Cardiovasc Risk. 1994;  1 173-178
    PubMedGoogle Scholar
  • 7 Buga G M, Gold M E, Fukuto J M, Ignarro L J. Shear stress-induced release of nitric oxide from endothelial cells grown on beads.  Hypertension. 1991;  17 187-193
    PubMedGoogle Scholar
  • 8 Castillo L, Chapman T E, Sanchez M, Yu Y, Burke J F, Ajami A M, Vogt J, Young V R. Plasma arginine and citrulline kinetics in adults given adequate and arginine-free diets.  Proc Natl Acad Sci USA. 1993;  90 7749-7753
    PubMedGoogle Scholar
  • 9 Castillo L, Sanchez M, Vogt J, Chapman T, DeRojas-Walker D C, Tannenbaum S R, Ajami A, Young V R. Plasma arginine, citrulline, and ornithine kinetics in adults, with observations on nitric oxide synthesis.  Am J Physiol. 1995;  268 370
    PubMedGoogle Scholar
  • 10 Duncker D J, Van Zon N S, Altman J D, Oavek T J, Bache R J. Role of K+ ATP channels in coronary vasodilation during exercise.  Circulation. 1993;  88 1245-1253
    PubMedGoogle Scholar
  • 11 Dyke C K, Proctor D N, Dietz N M, Joyner M J. Role of nitric oxide in exercise hyperaemia during prolonged rhythmic handgripping in humans.  J Appl Physiol. 1995;  488 259-265
    PubMedGoogle Scholar
  • 12 Fryburg D A. N G-Monomethy-L-arginine inhibits the blood flow but not the insulin-like response of forearm muscle to IGF-I.  J Clin Invest. 1996;  97 1319-1328
    PubMedGoogle Scholar
  • 13 Gilligan D, Panza J A, Kilcoyne C M, Waclawiw M A, Casino P R, Quyyumi A A. Contribution of endothelium-derived nitric oxide to exercise-induced vasodilation.  Circulation. 1994;  90 2853-2858
    PubMedGoogle Scholar
  • 14 Gonnewardene I P, Karim F. Attenuation of exercise vasodilatation by adenosine deaminase in anesthetized dogs.  J Physiol. 1991;  442 65-79
    PubMedGoogle Scholar
  • 15 Hevel J, Marletta M A. Nitric-oxide synthase assays.  Methods in Enzymol. 1994;  233 250-258
    PubMedGoogle Scholar
  • 16 Hibbs J B, Taintor R R, Vavrin Z. Macrophage cytotoxicity: role for L-arginine deaminase activity and imino nitrogen oxidation to nitrite.  Science. 1987;  235 473-476
    CrossrefPubMedGoogle Scholar
  • 17 Hickner R C, Fisher J S, Ehsani A A, Kohrt W M. Role of nitric oxide in skeletal muscle blood flow at rest and during dynamic exercise in humans.  Am J Physiol. 1997;  273 410
    PubMedGoogle Scholar
  • 18 Hishikawa K, Toshio N, Suzuki H, Kato R, Saruta T. Role of L-arginine-nitric oxide pathway in hypertension.  J Hypertension. 1993;  11 639-645
    PubMedGoogle Scholar
  • 19 Hogikyan R V, Supiano M A. Homologous upregulation of human arterial α-adrenergic responses by guanadrel.  J Clin Invest. 1993;  91 1429-1435
    PubMedGoogle Scholar
  • 20 Honig C R, Frierson J L. Role of adenosine in exercise vasodilation in dog gracilis muscle.  Am J Physiol. 1980;  238 715
    PubMedGoogle Scholar
  • 21 Ignarro L J, Fukuto J M, Griscavage J M, Rogers N E, Byrns R E. Oxidation of nitric oxide in aqueous solution to nitrite but not nitrate: comparison with enzymatically formed nitric oxide from L-arginine.  Proc Natl Acad Sci. 1993;  90 8103-8107
    PubMedGoogle Scholar
  • 22 Jia L, Bonaventura J, Stamler J S. S-nitrosohaemoglobin: A dynamic activity of blood involved in vascular control.  Nature. 1996;  380 221-226
    CrossrefPubMedGoogle Scholar
  • 23 Jungersten L, Ambring A, Wall B, Wennmalm A. Both physical fitness and acute exercise regulate nitric oxide formation in healthy humans.  Appl J Physiol. 1997;  82 760-764
    PubMedGoogle Scholar
  • 24 Kilbom A, Wennmalm A. Endogenous prostaglandins as local regulators of blood flow in man: effect of indomethacin on reactive and functional hyperemia.  J Physiol. 1976;  257 109-121
    PubMedGoogle Scholar
  • 25 Kingwell B A, Sherrard B, Jennings G L, Dart A M. Four weeks of cycle training increases basal production of nitric oxide from the forearm.  Am J Physiol. 1997;  272 1077
    PubMedGoogle Scholar
  • 26 Kobzik L, Reid M B, Bredt D S, Stamler J S. Nitric oxide in skeletal muscle.  Nature. 1994;  372 546-548
    CrossrefPubMedGoogle Scholar
  • 27 Kumagai K, Suzuki H, Ichikawa M, Jimbo M, Murakami M. Nitric oxide increases renal blood flow by interacting with the sympathetic nervous system.  Hypertension. 1994;  24 220-226
    PubMedGoogle Scholar
  • 28 Linder L, Kiowski W, Buhler F R, Luscher T F. Indirect evidence for release of endothelium-derived relaxing factor in human forearm circulation in vivo.  Circulation. 1990;  81 1762-1767
    CrossrefPubMedGoogle Scholar
  • 29 Lindstrom M J, Bates D M. Newton-Raphson and EM algorithms for linear mixed-effects models for repeated-measures data.  J Am Statistical Assoc. 1998;  83 1014-1022
    PubMedGoogle Scholar
  • 30 Marletta M, Yoon P S, Lynegar R, Leaf C D, Wishnok J S. Macrophage oxidation of L-arginine to nitrate and nitrite: nitric oxide is an intermediate.  Biochemistry. 1988;  27 8706-8711
    CrossrefPubMedGoogle Scholar
  • 31 McMahon T J, Hood J S, Kadowitz P J. Pulmonary vasodilator response to vagal stimulation is blocked by Nω-nitro-L-arginine methyl ester in the cat.  Circ Res. 1992;  70 364-369
    PubMedGoogle Scholar
  • 32 Miller V M, Vanhoutte P M. Enhanced release of endothelium-derived factor(s) by chronic increases in blood flow.  Am J Physiol. 1988;  255 451
    PubMedGoogle Scholar
  • 33 Node K, Kitakaz M, Sato H, Koretsune Y, Katsube Y, Karita M, Kosaka H, Hiroaki K, Masatsugu H. Effect of acute dynamic exercise on circulating plasma nitric oxide level and correlation to norephinephrine release in normal subjects.  Am J Cardiol. 1997;  79 526-528
    CrossrefPubMedGoogle Scholar
  • 34 Palmer R MJ, Moncada S. A novel citrulline-forming enzyme implicated in the formation of nitric oxide by vascular endothelial cells.  Biochem Biophys Res Commun. 1989;  158 348-352
    CrossrefPubMedGoogle Scholar
  • 35 Poveda J J, Riestra A, Salas E, Cagigas M L, Lopez-Somoza C, Amado J A, Berrazueta J R. Contribution of nitric oxide to exercise-induced changes in healthy volunteers: effects of acute exercise and long-term physical training.  Eur J Clin Invest. 1997;  27 967-971
    CrossrefPubMedGoogle Scholar
  • 36 Rubanyi G, Romero C, Vanhoutte P M. Flow-induced release of endothelium-derived relaxing factor.  Am J Physiol. 1986;  250 1149
    PubMedGoogle Scholar
  • 37 Shoemaker J K, Naylor H L, Pozeg Z I, Hughson R L. Failure of prostaglandins to modulate the time course of blood flow during dynamic forearm exercise in humans.  J Appl Physiol. 1996;  81 1516-1521
    PubMedGoogle Scholar
  • 38 Shoemaker J K, Halliwill J R, Hughson R L, Joyner M J. Contribution of acetylcholine and nitric oxide to forearm blood flow at exercise onset and recovery.  Am J Physiol. 1997;  273 2395
    PubMedGoogle Scholar
  • 39 Shultz P J, Tolins J P. Adaptation to increased dietary salt intake in the rat.  J Clin Invest. 1993;  91 642-650
    PubMedGoogle Scholar
  • 40 Smulders R A, Stehouwer C DA, Olthof C G, van Kamp G I, Teerlink T, De Vries M JM, Donker A JM. Plasma endothelin levels and vascular effects of intravenous L-arginine infusion in subjects with uncomplicated insulin-dependent diabetes mellitus.  Clin Sci. 1994;  87 37-43
    PubMedGoogle Scholar
  • 41 Tsikas D, Gutzki F M, Rossa S, Bauer H, Neumann C, Dockendorff K, Sandman J, Frolich J C. Measurement of nitrite and nitrate in biological fluids by gas chromatography-mass spectrometry and by the Griess assay: problems with the griess assay-solutions by gas chromatography-mass spectrometry.  Anal Biochem. 1997;  244 208-220
    CrossrefPubMedGoogle Scholar
  • 42 Vallance P, Collier J, Moncada S. Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man.  Lancet. 1989;  2 997-1000
    PubMedGoogle Scholar
  • 43 Wilson J, Kapoor S. Contribution of endothelium-derived relaxing factor to exercise-induced vasodilation in humans.  J Appl Physiol. 1993;  75 2740-2744
    PubMedGoogle Scholar
  • 44 Worthen H G, Liu H. Automatic pre-column derivitization and reversed-phase high performance liquid chromatography of primary and secondary amino acids in plasma with photo-diode array and fluorescence detection.  J Liquid Chromatography. 1992;  15 3323-3341
    PubMedGoogle Scholar

Ph.D. Michael D. Brown

Department of Kinesiology University of Maryland

College Park

Maryland

USA

Phone: + 1 (301) 4052483

Fax: + 1 (301) 3149167

Email: mb166@umail.umd.edu

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