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Dietary Nitrate and Skeletal Muscle Contractile Function in Heart Failure

  • Pathophysiology: Neuroendocrine, Vascular, and Metabolic Factors (S Katz, Section Editor)
  • Published:
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Abstract

Heart failure (HF) patients suffer from exercise intolerance that diminishes their ability to perform normal activities of daily living and hence compromises their quality of life. This is due largely to detrimental changes in skeletal muscle mass, structure, metabolism, and function. This includes an impairment of muscle contractile performance, i.e., a decline in the maximal force, speed, and power of muscle shortening. Although numerous mechanisms underlie this reduction in contractility, one contributing factor may be a decrease in nitric oxide (NO) bioavailability. Consistent with this, recent data demonstrate that acute ingestion of NO3 −-rich beetroot juice, a source of NO via the NO synthase-independent enterosalivary pathway, markedly increases maximal muscle speed and power in HF patients. This review discusses the role of muscle contractile dysfunction in the exercise intolerance characteristic of HF, and the evidence that dietary NO3 − supplementation may represent a novel and simple therapy for this currently underappreciated problem.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Heart disease and stroke statistics—2015 update: a report from the American Heart Association. Circulation. 2015;131:e29–322.

    Article  PubMed  Google Scholar 

  2. Zizola C, Schulze PC. Metabolic and structural impairment of skeletal muscle in heart failure. Heart Fail Rev. 2013;18:623–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Okita K, Kinugawa S, Tsutsui H. Exercise intolerance in chronic heart failure. Skeletal muscle dysfunction and potential therapies. Circ J. 2013;77:293–300. This article summarizes research demonstrating the importance of skeletal muscle abnormalities to the exercise intolerance that accompanies HF.

    Article  CAS  PubMed  Google Scholar 

  4. Bhella PS, Prasad A, Heinicke K, Hastings JL, Arbab-Zadeh A, Adams-Heut B, et al. Abnormal hemodynamic response to exercise in heart failure with preserved ejection fraction. Eur J Heart Fail. 2011;13:1296–304.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Haykowsky MJ, Kouba EJ, Brubaker PH, Nicklas BJ, Eggebeen J, Kitzman DW. Skeletal muscle composition and its relation to exercise tolerance in older patients with heart failure and preserved ejection fraction. Am J Cardiol. 2014;113:1211–6.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Kitzman DW, Nicklas B, Kraus WE, Lyles MF, Eggebeen J, Morgan TW, et al. Skeletal muscle abnormalities and exercise intolerance in older patients with heart failure and preserved ejection fraction. Am J Heart Circ Physiol. 2014;306:H1364–70.

    Article  CAS  Google Scholar 

  7. Mancini DM, Coyle EF, Coggan AR, Beltz J, Ferraro N, Montain S, et al. Contribution of intrinsic skeletal muscle changes to 31P NMR abnormalities in patients with chronic heart failure. Circulation. 1989;80:1338–46.

    Article  CAS  PubMed  Google Scholar 

  8. Sullivan MJ, Green HJ, Cobb FR. Skeletal muscle biochemistry and histology in ambulatory patients with long term heart failure. Circulation. 1990;81:518–27.

    Article  CAS  PubMed  Google Scholar 

  9. Schaufelberger M, Eriksson BO, Grimby G, Held P, Swedberg K. Skeletal muscle fiber composition and capillarization in patients with chronic heart failure: relation to exercise capacity and central hemodynamics. J Card Fail. 1995;1:267–72.

    Article  CAS  PubMed  Google Scholar 

  10. Massie BM, Simoni A, Sahgal P, Wells L, Dudley GA. Relation of systemic and local muscle exercise capacity to skeletal muscle characteristics in men with congestive heart failure. J Am Coll Cardiol. 1996;27:140–5.

    Article  CAS  PubMed  Google Scholar 

  11. Sullivan MJ, Duscha BD, Klitgaard H, Kraus WE, Cobb FR, Saltin B. Altered expression of myosin heavy chain in human skeletal muscle in chronic heart failure. Med Sci Sports Exerc. 1997;29:860–6.

  12. Drexler H, Riede U, Munzel T, Konig H, Funke E, Just H. Alterations of skeletal muscle in chronic heart failure. Circulation. 1992;85:1751–9.

    Article  CAS  PubMed  Google Scholar 

  13. Wiener DH, Fink LI, Maris J, Jones RA, Chance B, Wilson JR. Abnormal skeletal muscle bioenergetics during exercise in patients with heart failure: role of reduced muscle blood flow. Circulation. 1986;73:1127–36.

    Article  CAS  PubMed  Google Scholar 

  14. Maskin CS, Forman R, Sonnenblick EH, Frishman WH, LeJemtel TH. Failure of dobutamine to increase exercise capacity despite hemodynamic improvement in severe chronic heart failure. Am J Cardiol. 1983;51:177–82.

    Article  CAS  PubMed  Google Scholar 

  15. Okita K, Yonezawa K, Nishijima H, Hanada A, Ohtsubo M, Kohya T, et al. Skeletal muscle metabolism limits exercise capacity in patients with chronic heart failure. Circulation. 1998;98:1886–91.

    Article  CAS  PubMed  Google Scholar 

  16. Wilson JR, Martin JL, Ferraro N. Impaired skeletal muscle nutritive flow during exercise in patients with congestive heart failure: role of cardiac pump dysfunction as determined by the effect of dobutamine. Am J Cardiol. 1984;53:1308–15.

    Article  CAS  PubMed  Google Scholar 

  17. Minotti JR, Christoph I, Oka R, Weiner MW, Wells L, Massie BM. Impaired skeletal muscle function in patients with congestive heart failure. Relationship to systemic exercise performance. J Clin Invest. 1991;88:2077–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Hanada A, Okita K, Yonezawa K, Ohtsubo M, Kohya T, Murakami T, et al. Dissociation between muscle metabolism and oxygen kinetics during recovery from exercise in patients with chronic heart failure. Heart. 2000;83:161–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Mancini DM, Schwartz M, Ferraro N, Seestedt R, Chance B, Wilson JR. Effect of dobutamine on skeletal muscle metabolism in patients with congestive heart failure. Am J Cardiol. 1990;65:1121–6.

    Article  CAS  PubMed  Google Scholar 

  20. Olson TP, Joyner MJ, Eisenach JH, Curry TB, Johnson BD. Influence of locomotor muscle afferent inhibition on the ventilator response to exercise in heart failure. Exp Physiol. 2014;99:414–26.

    Article  PubMed  Google Scholar 

  21. Schaufelberger M, Eriksson BO, Lönn L, Rundqvist SKS, Swedbert K. Skeletal muscle characteristics, muscle strength and thigh muscle area in patients before and after cardiac transplantation. Eur J Heart Fail. 2001;3:59–67.

    Article  CAS  PubMed  Google Scholar 

  22. Quittan M, Sturm B, Wiesinger GF, Fialka-Moser V, Pacher R, Rӧdler S. Skeletal muscle strength following orthotopic heart transplantation. Wien Klin Wochenschr. 1999;111:467–83.

    Google Scholar 

  23. Buller NP, Jones D, Poole-Wilson PA. Direct measurement of skeletal muscle fatigue in patients with chronic heart failure. Br Heart J. 1991;65:20–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Magnusson G, Isberg B, Karlberg K, Sylvén C. Skeletal muscle strength and endurance in chronic congestive heart failure secondary to idiopathic dilated cardiomyopathy. Am J Cardiol. 1994;73:307–9.

    Article  CAS  PubMed  Google Scholar 

  25. Harridge SDR, Magnusson G, Gordon A. Skeletal muscle contractile characteristics and fatigue resistance in patients with chronic heart failure. Eur Heart J. 1996;17:896–901.

    Article  CAS  PubMed  Google Scholar 

  26. Harrington D, Anker SD, Chua TP, Webb-Peploe KM, Ponikowski PP, Poole-Wilson PA, et al. Skeletal muscle function and its relation to exercise tolerance in chronic heart failure. JACC. 1997;30:1758–64.

    Article  CAS  PubMed  Google Scholar 

  27. Clark A, Rafferty D, Arbuthnott K. Relationship between isokinetic muscle strength and exercise capacity in chronic heart failure. Int J Cardiol. 1997;59:145–8.

    Article  CAS  PubMed  Google Scholar 

  28. Sunnerhagen KS, Cider A, Shcaufelberger M, Hedberg M, Grimby G. Muscular performance in heart failure. J Card Fail. 1998;4:97–104.

    Article  CAS  PubMed  Google Scholar 

  29. Carrington CA, Fisher WK, Davies MK, White MJ. Is there a relationship between muscle fatigue resistance and cardiovascular responses to isometric exercise in mild chronic heart failure? Eur J Heart Fail. 2001;3:53–8.

    Article  CAS  PubMed  Google Scholar 

  30. Brunjes DL, Dunlop M, Wu C, Jones M, Kato TS, Kennel PJ, Armstrong HF, Choo TH, Bartels MN, Forman DE, Mancini DM, Schulze PC. Analysis of skeletal muscle torque capacity and circulating ceramides in patients with advanced heart failure. J Card Fail. 2016. doi:10.1016/j.cardfail.2016.02.002. [Epub ahead of print].

  31. Pannizolo FA, Mairorana AJ, Naylor LH, Dembo L, Lloyd DG, Green DJ, et al. Gait analysis in chronic heart failure: the calf as a locus of impaired walking capacity. J Biomech. 2014;47:3719–25.

    Article  Google Scholar 

  32. Panizzolo FA, Maiorana AJ, Naylor LH, Lichtwark GA, Dembo L, Lloyd DG, et al. Is the soleus a sentinel muscle for impaired aerobic capacity in heart failure? Med Sci Sports Exerc. 2015;47:498–508.

    Article  PubMed  Google Scholar 

  33. Rehn TA, Munkvik M, Lunde PK, Sjaastad I, Sejersted OM. Intrinsic skeletal muscle alterations in chronic heart failure: a disease-specific myopathy or a result of deconditioning? Heart Fail Rev. 2012;17:421–36.

    Article  CAS  PubMed  Google Scholar 

  34. Toth MJ, Shaw AO, Miller MS, VanBuren P, LeWinter MM, Maughan DW, et al. Reduced knee extensor function in heart failure is not explained by inactivity. Int J Cardiol. 2010;143:276–82.

    Article  PubMed  Google Scholar 

  35. Suzuki K, Omiya K, Yamada S, Kobayashi T, Suzuki N, Osada N, et al. Relations between strength and endurance of leg skeletal muscle and cardiopulmonary exercise testing parameters in patients with chronic heart failure. J Cardiol. 2004;43:59–68.

    PubMed  Google Scholar 

  36. Senden PJ, Sabelis LWE, Zonderland ML, van de Kolk R, Meiss L, de Vries WR, et al. Determinants of maximal exercise performance in chronic heart failure. Eur J Cardiovasc Prev Rehabil. 2004;11:41–7.

    Article  PubMed  Google Scholar 

  37. Levinger I, Bronks R, Cody DV, Linton I, Davie A. Resistance training for chronic heart failure patients on beta blocker medications. Int J Cardiol. 2005;102:493–9.

    Article  PubMed  Google Scholar 

  38. Delagardelle C, Feiereisen P, Krecke R, Essamri B, Beissel J. Objective of 6 months’ endurance and strength training program in outpatients with congestive heart failure. Med Sci Sports Exerc. 1999;31:1102–7.

    Article  CAS  PubMed  Google Scholar 

  39. Savage P, Shaw AO, Miller MS, VanBuren P, LeWinter M, Ades PA, et al. Effect of resistance training on physical disability in chronic heart failure. Med Sci Sports Exerc. 2011;43:1379–86.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Hülsmann M, Quittan M, Berger R, Crevenna R, Springer C, Nuhr M, et al. Muscle strength as a predictor of long-term survival in severe congestive heart failure. Eur J Heart Fail. 2004;6:101–7.

    Article  PubMed  Google Scholar 

  41. Toth MJ, Ades PA, Tischler MD, Tracy RP, LeWinter MM. Immune activation is associated with reduced skeletal muscle mass and physical function in chronic heart failure. Int J Cardiol. 2006;109:179–87.

    Article  PubMed  Google Scholar 

  42. Szentesi P, Bekedam MA, van Beek-Harmsen BJ, van der Laarse WJ, Zaremba R, Boonstra A, et al. Depression of force production and ATPase activity in different types of human skeletal muscle fibers from patients with chronic heart failure. J Appl Physiol. 2005;99:2189–95.

    Article  CAS  PubMed  Google Scholar 

  43. Miller MS, van Buren P, LeWinter MM, Lecker SH, Selby DE, Palmer BM, et al. Mechanisms underlying skeletal muscle weakness in human heart failure. Alterations in single fiber myosin protein content and function. Circ Heart Fail. 2009;2:700–6.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Miller MS, VanBuren P, LeWinter MM, Braddock JM, Ades PA, Maughan DW, et al. Chronic heart failure decreases cross-bridge kinetics in single muscle fibers from humans. J Physiol. 2010;588:4039–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Toth MJ, Ward K, van der Velden J, Miller MS, VanBuren P, LeWinter MM, et al. Chronic heart failure reduces Akt phosphorylation in human skeletal muscle: relationship to muscle size and function. J Appl Physiol. 2011;110:892–900.

    Article  CAS  PubMed  Google Scholar 

  46. Rullman E, Andersson DC, Melin M, Reiken S, Mancini DM, Marks AR, et al. Modifications of skeletal muscle ryanodine receptor type I and exercise intolerance in heart failure. J Heart Lung Transplant. 2013;32:925–9.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Middlekauf HR, Vigna C, Verity MA, Fonarow GC, Horwich TB, Hamilton MA, et al. Abnormalities of calcium handling proteins in skeletal muscle mirror those the heart in humans with heart failure: a shared mechanism? J Card Fail. 2012;18:724–33.

    Article  Google Scholar 

  48. Andersson DC, Marks AR. Fixing ryanodine receptor Ca2+ leak—a novel therapeutic strategy for contractile failure in heart and skeletal muscle. Drug Discov Today Dis Mech. 2010;7:e151–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Godard MP, Whitman SA, Song Y-H, Delafontaine P. Skeletal muscle molecular alterations precede whole-muscle dysfunction in NYHA Class II heart failure patients. Clin Interv Aging. 2012;7:489–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Maréchal G, Gaily P. Effects of nitric oxide on the contraction of skeletal muscle. Cell Mol Life Sci. 1999;55:1088–102.

    Article  PubMed  Google Scholar 

  51. Kaminski HJ, Andrade FH. Nitric oxide: biologic effects on muscle and role in muscle diseases. Neuromuscul Disord. 2001;11:517–24.

    Article  CAS  PubMed  Google Scholar 

  52. Fulford J, Winyard PG, Vanhatalo A, Bailey SJ, Blackwell JR, Jones AM. Influence of dietary nitrate supplementation on human skeletal muscle metabolism and force production during maximum voluntary contractions. Pflugers Arch. 2013;465:517–28.

    Article  CAS  PubMed  Google Scholar 

  53. Evangelista AM, Rao VS, Filo AR, Marozkina NV, Doctor A, Jones DR, et al. Direct regulation of striated muscle myosins by nitric oxide and endogenous nitrosothiols. PLoS One. 2010;5, e11209.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Lamb GD, Westerblad H. Acute effects of reactive oxygen and nitrogen species on the contractile function of skeletal muscle. J Physiol. 2011;589:2119–27.

    Article  CAS  PubMed  Google Scholar 

  55. Hare JM, Stamler JS. NO/redox disequilibrium in the failing heart and cardiovascular system. J Clin Invest. 2005;115:509–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Haywood GA, Tsao PS, von der Leyen HE, Mann MJ, Keeling PJ, Trindade PT, et al. Expression of inducible nitric oxide synthase in human heart failure. Circulation. 1996;93:1087–94.

    Article  CAS  PubMed  Google Scholar 

  57. Adams V, Yu J, Mӧbius-Winkler S, Linke A, Weigl C, Hilbrich L, et al. Inducible nitric oxide synthase in skeletal muscle biopsies from patients with chronic heart failure. Biochem Mol Med. 1997;61:152–60.

    Article  CAS  PubMed  Google Scholar 

  58. Riede UN, Fӧrstermann U, Drexler H. Inducible nitric oxide synthase in skeletal muscle of patients with chronic heart failure. J Am Coll Cardiol. 1998;32:964–9.

    Article  CAS  PubMed  Google Scholar 

  59. Katz SD, Khan T, Zeballos GA, Mathew L, Potharlanka P, Knecht M, et al. Decreased activity of the L-arginine-nitric oxide metabolic pathway in patients with congestive heart failure. Circulation. 1999;99:2113–7.

    Article  CAS  PubMed  Google Scholar 

  60. Clini E, Volterrani M, Pagani M, Bianchi L, Porta R, Gile LS, et al. Endogenous nitric oxide in patients with chronic heart failure (CHF): relation to functional impairment and nitrate-containing therapies. Int J Cardiol. 2000;73:123–30.

    Article  CAS  PubMed  Google Scholar 

  61. Adachi H, Nguyen PH, Belardinelli R, Hunter D, Jung T, Wasserman K. Nitric oxide production during exercise in heart failure. Am Heart J. 1997;133:196–202.

    Article  Google Scholar 

  62. Busotti M, Andreini D, Agostoni P. Exercise-induced changes in exhaled nitric oxide in heart failure. Eur J Heart Fail. 2004;6:551–4.

    Article  Google Scholar 

  63. Lovell SL, Stevenson H, Young IS, McDowell G, McEneaney D, Riley MS, et al. Exhaled nitric oxide during incremental and constant workload exercise in chronic cardiac failure. Eur J Clin Invest. 2000;30:181–7.

    Article  CAS  PubMed  Google Scholar 

  64. Katz SD. The role of endothelium-derived vasoactive substances in the pathophysiology of exercise intolerance in patients with congestive heart failure. Prog Cardiovasc Dis. 1995;38:23–50.

    Article  CAS  PubMed  Google Scholar 

  65. Piknova B, Park JW, Swanson KM, Dey S, Noguchi CT, Schechter AN. Skeletal muscle as an endogenous nitrate reservoir. Nitric Oxide. 2015;47:10–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Piknova B, Park JW, Kwan K, Schecter AN. Nitrate as a source of nitrite and nitric oxide during exercise hyperemia in rat skeletal muscle. Nitric Oxide. 2016;55–56:54–61.

    Article  PubMed  Google Scholar 

  67. Omar SA, Webb AJ, Lundberg JO, Weitzberg E. Therapeutic effects of inorganic nitrate and nitrite in cardiovascular and metabolic diseases. J Intern Med. 2016;279:315–26. This comprehensive review summarizes recent animal and humans studies of the cardiovascular and metabolic effects of dietary nitrate.

    Article  CAS  PubMed  Google Scholar 

  68. Chirinos JA, Zamani P. The nitrate-nitrite-NO pathway and its implications for heart failure and preserved ejection fraction. Curr Heart Fail Rep. 2016;13:47–59. This recent review discusses the potential role of dietary nitrate as well as other compounds that target the nitrate-nitrite-NO pathway as a possible treatment for HF (particularly HF with preserved ejection fraction).

    Article  CAS  PubMed  Google Scholar 

  69. Li H, Kundu TK, Zweier JL. Characterization of the magnitude and mechanism of aldehyde oxidase-mediated nitric oxide production from nitrite. J Biol Chem. 2009;284:33850–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Cantu-Medellin N, Kelley EE. Xanthine oxidoreductase-catalyzed reduction of nitrite to nitric oxide: insights regarding where, when and how. Nitric Oxide. 2013;34:19–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Coggan AR, Leibowitz JL, Anderson Spearie C, Kadkhodayan A, Thomas DP, Ramamurthy S, et al. Acute dietary nitrate intake improves muscle contractile function in patients with heart failure: a double-blind, placebo-controlled, randomized trial. Circ Heart Fail. 2015;8:914–20. This small clinical trial demonstrated significant improvements in maximal muscle speed and power in HF patients following acute ingestion of dietary nitrate in the form of a concentrated beetroot juice supplement.

    Article  CAS  PubMed  Google Scholar 

  72. Coggan AR, Leibowitz JL, Kadkhodayan A, Thomas DT, Ramamurthy S, Anderson Spearie C, et al. Effect of acute dietary nitrate intake on maximal knee extensor speed and power in healthy men and women. Nitric Oxide. 2015;48:16–21. This was the first study to demonstrate that dietary nitrate enhances the contractile properties of human muscle during voluntary exercise.

    Article  CAS  PubMed  Google Scholar 

  73. Degache F, Garet M, Calmels P, Costes F, Barthélémy JC, Roche F. Enhancement of isokinetic muscle strength with a combined training programme in chronic heart failure. Clin Physiol Funct Imaging. 2007;25:225–30.

    Article  Google Scholar 

  74. Delagardelle C, Feiereisen P, Autier P, Shita R, Krecke R, Beissel J. Strength/endurance training versus endurance training in congestive heart failure. Med Sci Sports Exerc. 2002;34:1868–72.

    Article  PubMed  Google Scholar 

  75. Metra M, Giubbini R, Nodari S, Boldi E, Modena MG, Dei CL. Differential effects of beta-blockers in patients with heart failure: a prospective, randomized, double-blind comparison of the long-term effects of metoprolol versus carvedilol. Circulation. 2000;102:546–51.

    Article  CAS  PubMed  Google Scholar 

  76. Schellenbaum GD, Smith NL, Heckbert SR, Lumley T, Rea TD, Furberg CD, et al. Weight loss, muscle strength, and angiotensin-converting enzyme inhibitors in older adults with congestive heart failure or hypertension. J Am Geriatr Soc. 2005;53:1996–2000.

    Article  PubMed  Google Scholar 

  77. Kinugawa T, Osaki S, Kato M, Ogino K, Shimoyama M, Tomikura Y, et al. Effects of the angiotensin-converting enzyme inhibitor alacepril on exercise capacity and neurohormonal factors in patients with mild-to-moderate heart failure. Clin Exp Pharmacol Physiol. 2002;29:1060–5.

    Article  CAS  PubMed  Google Scholar 

  78. Edelmann F, Wachter R, Schmidt AG, Kraigher-Krainer E, Colantonio C, Kamke W, et al. Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved ejection fraction: the Aldo-Dhf Randomized Controlled Trial. JAMA. 2013;309:781–91.

    Article  CAS  PubMed  Google Scholar 

  79. Harrington D, Chua TP, Coats AJ. The effect of salbutamol on skeletal muscle in chronic heart failure. Int J Cardiol. 2000;73:257–65.

    Article  CAS  PubMed  Google Scholar 

  80. Kerley CP, O’Neill JO, Bijjam R, Blaine C, James PE, Comican L. Dietary nitrate increased exercise tolerance in patients with non-ischemic, dilated cardiomyopathy—a double-blind, randomized, placebo-controlled, crossover trial. J Heart Lung Transplant. 2016. doi:10.1016/j.healun.2016.01.018. [Epub ahead of print].

  81. Zamani P, Rawat D, Shiva-Kumar P, Geraci S, Bhuva R, Konda P, et al. Effect of inorganic nitrate on exercise capacity in heart failure with preserved ejection fraction. Circulation. 2015;131:371–80.

    Article  CAS  PubMed  Google Scholar 

  82. Borlaug BA, Koepp KE, Melenovsky V. Sodium nitrite improves exercise hemodynamics and ventricular performance in heart failure with preserved ejection fraction. J Am Coll Cardiol. 2015;66:1672–82.

    Article  CAS  PubMed  Google Scholar 

  83. Eggebeen J, Kim-Shapiro DB, Haykowsky M, Morgan TM, Basu S, Brubaker P, Rejeski J, Kitzman DW. One week of daily dosing with beetroot juice improves submaximal endurance and blood pressure in older patients with heart failure and preserved ejection fraction. JACC Heart Fail. 2016. doi:10.1016/j.jchf.2015.12.013. [Epub ahead of print].

  84. Hernández A, Schiffer TA, Ivarsson N, Cheng AJ, Bruton JD, Lundberg JO, et al. Dietary nitrate increases tetanic [Ca2+]I and contractile force in mouse fast-twitch muscle. J Physiol. 2012;590:3575–83.

    Article  PubMed  PubMed Central  Google Scholar 

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  1. Cardiovascular Imaging Laboratory, Mallinckrodt Institute of Radiology, Department of Radiology, Washington University School of Medicine, 510 S. Kingshighway Blvd. – Campus Box 8225, St. Louis, MO, 63110, USA

    Andrew R. Coggan & Linda R. Peterson

  2. Cardiovascular Division, Department of Internal Medicine, Washington University School of Medicine, 660 S. Euclid Ave. – Campus Box 8086, St. Louis, MO, 63110, USA

    Linda R. Peterson

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Correspondence to Andrew R. Coggan.

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Dr. Coggan reports grants from the Institute for Clinical and Translational Sciences and the Barnes-Jewish Hospital Foundation during the conduct of the study.

Dr. Peterson reports grants from the Institute of Clinical and Translational Sciences and the Barnes-Jewish Hospital Foundation during the conduct of the study; and other relevant financial activities outside the submitted work from Merck, Johnson and Johnson, Medronic, and Gilead.

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This article is part of the Topical Collection on Pathophysiology: Neuroendocrine, Vascular, and Metabolic Factors

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Coggan, A.R., Peterson, L.R. Dietary Nitrate and Skeletal Muscle Contractile Function in Heart Failure. Curr Heart Fail Rep 13, 158–165 (2016). https://doi.org/10.1007/s11897-016-0293-9

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