Skeletal muscle blood flow and oxygen uptake at rest and during exercise in humans: A pet study with nitric oxide and cyclooxygenase inhibition

American Journal of Physiology - Heart and Circulatory Physiology

Volumn 300, Issue 4, 2011, Pages

  Ilkka, Heinonen ^a   Bengt, Saltin ^c   Jukka, Kemppainen ^a   Sipilä, Hannu T ^a   Vesa, Oikonen ^a   Pirjo, Nuutila ^a   Juhani, Knuuti ^a   Kari, Kalliokoski ^a   Ylva, Hellsten ^b  

^a TURKU UNIVERSITY HOSPITAL   (Finland)

^b UNIVERSITY OF COPENHAGEN   (Denmark)

^c UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

Blood flow; Nitric oxide; Oxygen consumption; Skeletal muscle

Indexed keywords

INDOMETACIN; N(G) METHYLARGININE; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; NITRIC OXIDE SYNTHASE INHIBITOR; OXYGEN 15; PROSTAGLANDIN SYNTHASE; PROSTAGLANDIN SYNTHASE INHIBITOR; PROSTANOID; WATER O 15;

ADULT; ARTICLE; BLOOD OXYGEN TENSION; BLOOD SAMPLING; CONTROLLED STUDY; DRUG INFUSION; DRUG INHIBITION; ENZYME INHIBITION; EXERCISE; HUMAN; HUMAN EXPERIMENT; LIGHT KNEE EXTENSOR EXERCISE; LIMB; MALE; MICROCIRCULATION; MUSCLE BLOOD FLOW; NORMAL HUMAN; OXYGEN CONSUMPTION; OXYGEN EXTRACTION FRACTION; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; QUADRICEPS FEMORIS MUSCLE; REST; SKELETAL MUSCLE;

ADULT; BLOOD PRESSURE; CYCLOOXYGENASE INHIBITORS; ENZYME INHIBITORS; EXERCISE; HEART RATE; HUMANS; INDOMETHACIN; KNEE; MALE; MUSCLE, SKELETAL; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; OMEGA-N-METHYLARGININE; OXYGEN; OXYGEN CONSUMPTION; POSITRON-EMISSION TOMOGRAPHY; PROSTAGLANDINS; REGIONAL BLOOD FLOW; REST; VASCULAR RESISTANCE; YOUNG ADULT;

EID: 79955064936     PISSN: 03636135     EISSN: 15221539     Source Type: Journal    
DOI: 10.1152/ajpheart.00996.2010     Document Type: Article

References (38)

1. Ardilouze JL, Fielding BA, Currie JM, Frayn KN, Karpe F. Nitric oxide and beta-adrenergic stimulation are major regulators of preprandial and postprandial subcutaneous adipose tissue blood flow in humans. Circulation 109: 47-52, 2004.
2. Boushel R, Langberg H, Gemmer C, Olesen J, Crameri R, Scheede C, Sander M, Kjaer M. Combined inhibition of nitric oxide and prostaglandins reduces human skeletal muscle blood flow during exercise. J Physiol 543: 691-698, 2002.
3. Brown GC. Nitric oxide and mitochondrial respiration. Biochim Biophys Acta 1411: 351-369, 1999.
4. Brown GC. Regulation of mitochondrial respiration by nitric oxide inhibition of cytochrome c oxidase. Biochim Biophys Acta 1504: 46-57, 2001.
5. Brown GC, Cooper CE. Nanomolar concentrations of nitric oxide reversibly inhibit synaptosomal respiration by competing with oxygen at cytochrome oxidase. FEBS Lett 356: 295-298, 1994.
6. Cleeter MW, Cooper JM, Darley-Usmar VM, Moncada S, Schapira AH. Reversible inhibition of cytochrome c oxidase, the terminal enzyme of the mitochondrial respiratory chain, by nitric oxide. Implications for neurodegenerative diseases. FEBS Lett 345: 50-54, 1994.
7. Coffman JD. Effects of endothelium-derived nitric oxide on skin and digital blood flow in humans. Am J Physiol Heart Circ Physiol 267: H2087-H2090, 1994.
8. Cooper CE, Giulivi C. Nitric oxide regulation of mitochondrial oxygen consumption II: Molecular mechanism and tissue physiology. Am J Physiol Cell Physiol 292: C1993-C2003, 2007.
9. Erusalimsky JD, Moncada S. Nitric oxide and mitochondrial signaling: from physiology to pathophysiology. Arterioscler Thromb Vasc Biol 27: 2524-2531, 2007.
10. Frandsenn U, Bangsbo J, Sander M, Hoffner L, Betak A, Saltin B, Hellsten Y. Exercise-induced hyperaemia and leg oxygen uptake are not altered during effective inhibition of nitric oxide synthase with N(G)-nitro-L-arginine methyl ester in humans. J Physiol 531: 257-264, 2001.
11. Goldsmith PC, Leslie TA, Hayes NA, Levell NJ, Dowd PM, Foreman JC. Inhibitors of nitric oxide synthase in human skin. J Invest Dermatol 106: 113-118, 1996.
12. Heinonen I, Kemppainen J, Kaskinoro K, Peltonen JE, Borra R, Lindroos MM, Oikonen V, Nuutila P, Knuuti J, Hellsten Y, Boushel R, Kalliokoski KK. Comparison of exogenous adenosine and voluntary exercise on human skeletal muscle perfusion and perfusion heterogeneity. J Appl Physiol 108: 378-386, 2010.
13. Heinonen IH, Kemppainen J, Kaskinoro K, Peltonen JE, Borra R, Lindroos M, Oikonen V, Nuutila P, Knuuti J, Boushel R, Kalliokoski KK. Regulation of human skeletal muscle perfusion and its heterogeneity during exercise in moderate hypoxia. Am J Physiol Regul Integr Comp Physiol 299: R72-R79, 2010.
14. Heinonen IH, Nesterov SV, Kemppainen JT, Nuutila P, Knuuti J, Laitio R, Kjaer M, Boushel R, Kalliokoski KK. Role of adenosine in regulating the heterogeneity of skeletal muscle blood flow during exercise in humans. J Appl Physiol 103: 2042-2048, 2007.
15. Hillig T, Krustrup P, Fleming I, Osada T, Saltin B, Hellsten Y. Cytochrome P450 2C9 plays an important role in the regulation of exercise-induced skeletal muscle blood flow and oxygen uptake in humans. J Physiol 546: 307-314, 2003.
16. Iida H, Kanno I, Miura S, Murakami M, Takahashi K, Uemura K. Error analysis of a quantitative cerebral blood flow measurement using H2(15)O autoradiography and positron emission tomography, with respect to the dispersion of the input function. J Cereb Blood Flow Metab 6: 536-545, 1986.
17. Jacob M, Bjarnason I, Rafi S, Wrigglesworth J, Simpson RJ. A study of the effects of indometacin on liver mitochondria from rats, mice and humans. Aliment Pharmacol Ther 15: 1837-1842, 2001.
18. Kalliokoski KK, Laaksonen MS, Takala TO, Knuuti J, Nuutila P. Muscle oxygen extraction and perfusion heterogeneity during continuous and intermittent static exercise. J Appl Physiol 94: 953-958, 2003.
19. Kalliokoski KK, Langberg H, Ryberg AK, Scheede-Bergdahl C, Doessing S, Kjaer A, Kjaer M, Boushel R. Nitric oxide and prostaglandins influence local skeletal muscle blood flow during exercise in humans: coupling between local substrate uptake and blood flow. Am J Physiol Regul Integr Comp Physiol 291: R803-R809, 2006.
20. Krause MM, Brand MD, Krauss S, Meisel C, Vergin H, Burmester GR, Buttgereit F. Nonsteroidal antiinflammatory drugs and a selective cyclooxygenase 2 inhibitor uncouple mitochondria in intact cells. Arthritis Rheum 48: 1438-1444, 2003.
21. Levy BI, Schiffrin EL, Mourad JJ, Agostini D, Vicaut E, Safar ME, Struijker-Boudier HA. Impaired tissue perfusion: a pathology common to hypertension, obesity, and diabetes mellitus. Circulation 118: 968-976, 2008.
22. Moncada S, Erusalimsky JD. Does nitric oxide modulate mitochondrial energy generation and apoptosis? Nat Rev Mol Cell Biol 3: 214-220, 2002.
23. Mortensen SP, Gonzalez-Alonso J, Damsgaard R, Saltin B, Hellsten Y. Inhibition of nitric oxide and prostaglandins, but not endothelialderived hyperpolarizing factors, reduces blood flow and aerobic energy turnover in the exercising human leg. J Physiol 581: 853-861, 2007.
24. Mortensen SP, Nyberg M, Thaning P, Saltin B, Hellsten Y. Adenosine contributes to blood flow regulation in the exercising human leg by increasing prostaglandin and nitric oxide formation. Hypertension 53: 993-999, 2009.
25. Nicholson WT, Vaa B, Hesse C, Eisenach JH, Joyner MJ. Aging is associated with reduced prostacyclin-mediated dilation in the human forearm. Hypertension 53: 973-978, 2009.
26. Nuutila P, Peltoniemi P, Oikonen V, Larmola K, Kemppainen J, Takala T, Sipila H, Oksanen A, Ruotsalainen U, Bolli GB, Yki-Jarvinen H. Enhanced stimulation of glucose uptake by insulin increases exercise-stimulated glucose uptake in skeletal muscle in humans: studies using [15O]O2, [15O]H2O, [18F]fluoro-deoxy-glucose, and positron emission tomography. Diabetes 49: 1084-1091, 2000.
27. Radegran G, Saltin B. Nitric oxide in the regulation of vasomotor tone in human skeletal muscle. Am J Physiol Heart Circ Physiol 276: H1951-H1960, 1999.
28. Rees DD, Palmer RM, Moncada S. Role of endothelium-derived nitric oxide in the regulation of blood pressure. Proc Natl Acad Sci USA 86: 3375-3378, 1989.
29. Ruotsalainen U, Raitakari M, Nuutila P, Oikonen V, Sipila H, Teras M, Knuuti MJ, Bloomfield PM, Iida H. Quantitative blood flow measurement of skeletal muscle using oxygen-15- water and PET. J Nucl Med 38: 314-319, 1997.
30. Schrage WG, Eisenach JH, Joyner MJ. Ageing reduces nitric-oxideand prostaglandin-mediated vasodilatation in exercising humans. J Physiol 579: 227-236, 2007.
31. Schrage WG, Wilkins BW, Johnson CP, Eisenach JH, Limberg JK, Dietz NM, Curry TB, Joyner MJ. Roles of nitric oxide synthase and cyclooxygenase in leg vasodilation and oxygen consumption during prolonged low-intensity exercise in untrained humans. J Appl Physiol 109: 768-777, 2010.
32. Schweizer M, Richter C. Nitric oxide potently and reversibly deenergizes mitochondria at low oxygen tension. Biochem Biophys Res Commun 204: 169-175, 1994.
33. Shen W, Hintze TH, Wolin MS. Nitric oxide. An important signaling mechanism between vascular endothelium and parenchymal cells in the regulation of oxygen consumption. Circulation 92: 3505-3512, 1995.
34. Shen W, Xu X, Ochoa M, Zhao G, Bernstein RD, Forfia P, Hintze TH. Endogenous nitric oxide in the control of skeletal muscle oxygen extraction during exercise. Acta Physiol Scand 168: 675-686, 2000.
35. Shen W, Xu X, Ochoa M, Zhao G, Wolin MS, Hintze TH. Role of nitric oxide in the regulation of oxygen consumption in conscious dogs. Circ Res 75: 1086-1095, 1994.
36. Sipilä HT, Clark JC, Peltola O, Teräs M. An automatic [15O]-H2O production system for heart and brain studies. J Label Compounds Radiopharmaceut 44: S1066-S1068, 2001.
37. Vallance P, Collier J, Moncada S. Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man. Lancet 2: 997-1000, 1989.
38. Victor VM, Nunez C, D'Ocon P, Taylor CT, Esplugues JV, Moncada S. Regulation of oxygen distribution in tissues by endothelial nitric oxide. Circ Res 104: 1178-1183, 2009.