Download PDF
Horm Metab Res 2012; 44(07): 489-493
DOI: 10.1055/s-0032-1314787
Mini-Review
© Georg Thieme Verlag KG Stuttgart · New York

β2 Adrenoceptor Signaling-induced Muscle Hypertrophy from Blood Flow Restriction: Is There Evidence?

J. P. Loenneke
1   Department of Health and Exercise Science, University of Oklahoma, Norman, OK, USA
,
J. M. Wilson
2   Department of Health Sciences and Human Performance, University of Tampa, Tampa, FL, USA
,
R. S. Thiebaud
1   Department of Health and Exercise Science, University of Oklahoma, Norman, OK, USA
,
T. Abe
3   Department of Health, Exercise Science, and Recreation Management, University of Mississippi, Oxford, MS, USA
,
R. P. Lowery
2   Department of Health Sciences and Human Performance, University of Tampa, Tampa, FL, USA
,
M. G. Bemben
1   Department of Health and Exercise Science, University of Oklahoma, Norman, OK, USA
› Author Affiliations
Further Information

Publication History

received 28 March 2012

accepted 26 April 2012

Publication Date:
25 May 2012 (online)

Also available at
    Permissions and Reprints

Abstract

Skeletal muscle hypertrophy and increases in muscular function have been observed following low intensity/load exercise with blood flow restriction (BFR). The mechanisms behind these effects are largely unknown, but have been hypothesized to include a metabolic accumulation induced increase in muscle activation, elevations in growth hormone, and improvements in muscle protein balance. However, many of the aforementioned mechanisms are not present with BFR in the absence of exercise. In these situations, signaling through the β2 adrenoceptor has been hypothesized to possibly contribute to the positive muscle adaptions, possibly in concert with muscle cell swelling. Signaling through the β2 adrenoceptor has been shown to stimulate both muscle protein synthesis and an inhibition of protein degradation through increasing cyclic adenosine monophosphate (cAMP) or signaling via the Gβγ subunit, especially in situations where the basal rates of protein synthesis are already reduced. Every study that has investigated the catecholamine response to BFR in the absence of exercise or in combination with exercise has shown a significant increase above resting conditions. However, from the available evidence, it is unlikely that the norepinephrine response from BFR, particularly with exercise, is playing a prominent role with muscle adaptation in skeletal muscle that is not immobilized by a cast or joint injury.

Key words

catecholamines - norepinephrine - epinephrine
 

  • References

  • 1 Loenneke JP, Wilson JM, Marin PJ, Zourdos MC, Bemben MG. Low intensity blood flow restriction training: a meta-analysis. Eur J Appl Physiol 2012; 112: 1849-1859
    CrossrefPubMedSearch in Google Scholar
  • 2 Fry CS, Glynn EL, Drummond MJ, Timmerman KL, Fujita S, Abe T, Dhanani S, Volpi E, Rasmussen BB. Blood flow restriction exercise stimulates mTORC1 signaling and muscle protein synthesis in older men. J Appl Physiol 2010; 108: 1199-1209
    CrossrefPubMedSearch in Google Scholar
  • 3 Gundermann DM, Fry CS, Dickinson JM, Walker DK, Timmerman KL, Drummond MJ, Volpi E, Rasmussen BB. Reactive hyperemia is not responsible for stimulating muscle protein synthesis following blood flow restriction exercise. J Appl Physiol 2012; 112: 1520-1528
    CrossrefPubMedSearch in Google Scholar
  • 4 Fujita S, Abe T, Drummond MJ, Cadenas JG, Dreyer HC, Sato Y, Volpi E, Rasmussen BB. Blood flow restriction during low-intensity resistance exercise increases S6K1 phosphorylation and muscle protein synthesis. J Appl Physiol 2007; 103: 903-910
    CrossrefPubMedSearch in Google Scholar
  • 5 Burd NA, West DW, Staples AW, Atherton PJ, Baker JM, Moore DR, Holwerda AM, Parise G, Rennie MJ, Baker SK, Phillips SM. Low-load high volume resistance exercise stimulates muscle protein synthesis more than high-load low volume resistance exercise in young men. PLoS One 2010; 5: e12033
    CrossrefPubMedSearch in Google Scholar
  • 6 Yasuda T, Abe T, Brechue WF, Iida H, Takano H, Meguro K, Kurano M, Fujita S, Nakajima T. Venous blood gas and metabolite response to low-intensity muscle contractions with external limb compression. Metabolism 2010; 59: 1510-1519
    CrossrefPubMedSearch in Google Scholar
  • 7 Loenneke JP, Wilson GJ, Wilson JM. A Mechanistic Approach to Blood Flow Occlusion. Int J Sports Med 2010; 31: 1-4
    Thieme ConnectPubMedSearch in Google Scholar
  • 8 Rennie MJ, Wackerhage H, Spangenburg EE, Booth FW. Control of the size of the human muscle mass. Annu Rev Physiol 2004; 66: 799-828
    CrossrefPubMedSearch in Google Scholar
  • 9 Manini TM, Vincent KR, Leeuwenburgh CL, Lees HA, Kavazis AN, Borst SE, Clark BC. Myogenic and proteolytic mRNA expression following blood flow restricted exercise. Acta Physiol (Oxf) 2011; 201: 255-263
    CrossrefPubMedSearch in Google Scholar
  • 10 Loenneke JP, Fahs CA, Rossow LM, Abe T, Bemben MG. The anabolic benefits of venous blood flow restriction training may be induced by muscle cell swelling. Med Hypotheses 2012; 78: 151-154
    CrossrefPubMedSearch in Google Scholar
  • 11 Kubota A, Sakuraba K, Koh S, Ogura Y, Tamura Y. Blood flow restriction by low compressive force prevents disuse muscular weakness. J Sci Med Sport 2011; 14: 95-99
    CrossrefPubMedSearch in Google Scholar
  • 12 Kubota A, Sakuraba K, Sawaki K, Sumide T, Tamura Y. Prevention of disuse muscular weakness by restriction of blood flow. Med Sci Sports Exerc 2008; 40: 529-534
    PubMedSearch in Google Scholar
  • 13 Takarada Y, Takazawa H, Ishii N. Applications of vascular occlusion diminish disuse atrophy of knee extensor muscles. Med Sci Sports Exerc 2000; 32: 2035-2039
    CrossrefPubMedSearch in Google Scholar
  • 14 Kraemer WJ, Ratamess NA. Hormonal responses and adaptations to resistance exercise and training. Sports Med 2005; 35: 339-361
    CrossrefPubMedSearch in Google Scholar
  • 15 Lynch GS, Ryall JG. Role of beta-adrenoceptor signaling in skeletal muscle: implications for muscle wasting and disease. Physiol Rev 2008; 88: 729-767
    CrossrefPubMedSearch in Google Scholar
  • 16 Navegantes LC, Migliorini RH, do Carmo Kettelhut I. Adrenergic control of protein metabolism in skeletal muscle. Curr Opin Clin Nutr Metab Care 2002; 5: 281-286
    CrossrefPubMedSearch in Google Scholar
  • 17 Johnson M. Molecular mechanisms of beta(2)-adrenergic receptor function, response, and regulation. J Allergy Clin Immunol 2006; 117: 18-24 quiz 25
    CrossrefPubMedSearch in Google Scholar
  • 18 Mersmann HJ. Overview of the effects of beta-adrenergic receptor agonists on animal growth including mechanisms of action. J Anim Sci 1998; 76: 160-172
    PubMedSearch in Google Scholar
  • 19 Murga C, Fukuhara S, Gutkind JS. A novel role for phosphatidylinositol 3-kinase beta in signaling from G protein-coupled receptors to Akt. J Biol Chem 2000; 275: 12069-12073
    CrossrefPubMedSearch in Google Scholar
  • 20 Navegantes LC, Baviera AM, Kettelhut IC. The inhibitory role of sympathetic nervous system in the Ca2+-dependent proteolysis of skeletal muscle. Braz J Med Biol Res 2009; 42: 21-28
    PubMedSearch in Google Scholar
  • 21 Kumamoto T, Kleese WC, Cong JY, Goll DE, Pierce PR, Allen RE. Localization of the Ca(2+)-dependent proteinases and their inhibitor in normal, fasted, and denervated rat skeletal muscle. Anat Rec 1992; 232: 60-77
    CrossrefPubMedSearch in Google Scholar
  • 22 Wendt A, Thompson VF, Goll DE. Interaction of calpastatin with calpain: a review. Biol Chem 2004; 385: 465-472
    CrossrefPubMedSearch in Google Scholar
  • 23 Zhang X, Odom DT, Koo SH, Conkright MD, Canettieri G, Best J, Chen H, Jenner R, Herbolsheimer E, Jacobsen E, Kadam S, Ecker JR, Emerson B, Hogenesch JB, Unterman T, Young RA, Montminy M. Genome-wide analysis of cAMP-response element binding protein occupancy, phosphorylation, and target gene activation in human tissues. Proc Natl Acad Sci USA 2005; 102: 4459-4464
    CrossrefPubMedSearch in Google Scholar
  • 24 Berdeaux R, Goebel N, Banaszynski L, Takemori H, Wandless T, Shelton GD, Montminy M. SIK1 is a class II HDAC kinase that promotes survival of skeletal myocytes. Nat Med 2007; 13: 597-603
    CrossrefPubMedSearch in Google Scholar
  • 25 Molkentin JD, Black BL, Martin JF, Olson EN. Cooperative activation of muscle gene expression by MEF2 and myogenic bHLH proteins. Cell 1995; 83: 1125-1136
    CrossrefPubMedSearch in Google Scholar
  • 26 Brennesvik EO, Ktori C, Ruzzin J, Jebens E, Shepherd PR, Jensen J. Adrenaline potentiates insulin-stimulated PKB activation via cAMP and Epac: implications for cross talk between insulin and adrenaline. Cell Signal 2005; 17: 1551-1559
    CrossrefPubMedSearch in Google Scholar
  • 27 Bolster DR, Jefferson LS, Kimball SR. Regulation of protein synthesis associated with skeletal muscle hypertrophy by insulin-, amino acid- and exercise-induced signalling. Proc Nutr Soc 2004; 63: 351-356
    CrossrefPubMedSearch in Google Scholar
  • 28 Rommel C, Bodine SC, Clarke BA, Rossman R, Nunez L, Stitt TN, Yancopoulos GD, Glass DJ. Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways. Nat Cell Biol 2001; 3: 1009-1013
    CrossrefPubMedSearch in Google Scholar
  • 29 Tran H, Brunet A, Griffith EC, Greenberg ME. The many forks in FOXO’s road. Sci STKE 2003; 2003 RE5
    PubMedSearch in Google Scholar
  • 30 Iida H, Kurano M, Takano H, Kubota N, Morita T, Meguro K, Sato Y, Abe T, Yamazaki Y, Uno K, Takenaka K, Hirose K, Nakajima T. Hemodynamic and neurohumoral responses to the restriction of femoral blood flow by KAATSU in healthy subjects. Eur J Appl Physiol 2007; 100: 275-285
    CrossrefPubMedSearch in Google Scholar
  • 31 Iida H, Kurano M, Takano H, Oonuma H, Imuta H, Kubota N, Morita T, Meguro K, Sato Y, Abe T, Yamazaki T, Nakajima T. Can KAATSU be used for an orthostatic strss in astronauts?: A case study. Int J KAATSU Training Res 2006; 2: 45-52
    CrossrefPubMedSearch in Google Scholar
  • 32 Nakajima T, Iida H, Kurano M, Takano H, Morita T, Meguro K, Sato Y, Yamazaki Y, Kawashima S, Ohshima H, Tachibana S, Ishii N, Abe T. Hemodynamic responses to simulated weightlessness of 24-h head-down bed rest and KAATSU blood flow restriction. Eur J Appl Physiol 2008; 104: 727-737
    CrossrefPubMedSearch in Google Scholar
  • 33 Emerson Jr TE. Effects of angiotensin, epinephrine, norepinephrine, and vasopressin on venous return. Am J Physiol 1966; 210: 933-942
    PubMedSearch in Google Scholar
  • 34 Navegantes LC, Resano NM, Baviera AM, Migliorini RH, Kettelhut IC. Effect of sympathetic denervation on the rate of protein synthesis in rat skeletal muscle. Am J Physiol Endocrinol Metab 2004; 286: E642-E647
    CrossrefPubMedSearch in Google Scholar
  • 35 Barker D, Saito M. Autonomic innervation of receptors and muscle fibres in cat skeletal muscle. Proc R Soc Lond B Biol Sci 1981; 212: 317-332
    CrossrefPubMedSearch in Google Scholar
  • 36 Phillips SM, Glover EI, Rennie MJ. Alterations of protein turnover underlying disuse atrophy in human skeletal muscle. J Appl Physiol 2009; 107: 645-654
    PubMedSearch in Google Scholar
  • 37 Inagaki Y, Madarame H, Neya M, Ishii N. Increase in serum growth hormone induced by electrical stimulation of muscle combined with blood flow restriction. Eur J Appl Physiol 2011; 111: 2715-2721
    CrossrefPubMedSearch in Google Scholar
  • 38 Kubota N, Takano H, Tsutsumi T, Kaab S, Kurano M, Iida H, Yasuda T, Meguro K, Morita T, Sato Y, Kawashima S, Yamazaki Y, Ohshima H, Tachibana S, Ishii N, Abe T, Nakajima T. Resistance exercise combined with KAATSU during simulated weightlessness. Int J KAATSU Training Res 2008; 4: 9-15
    CrossrefPubMedSearch in Google Scholar
  • 39 Madarame H, Neya M, Ochi E, Nakazato K, Sato Y, Ishii N. Cross-transfer effects of resistance training with blood flow restriction. Med Sci Sports Exerc 2008; 40: 258-263
    CrossrefPubMedSearch in Google Scholar
  • 40 Madarame H, Sasaki K, Ishii N. Endocrine responses to upper- and lower-limb resistance exercises with blood flow restriction. Acta Physiol Hung 2010; 97: 192-200
    CrossrefPubMedSearch in Google Scholar
  • 41 Sato Y, Yoshitomi A, Abe T. Acute growth hormone response to low-intensity KAATSU resistance exercise: Comparison between arm and leg. Int J KAATSU Training Res 2005; 1: 45-50
    CrossrefPubMedSearch in Google Scholar
  • 42 Takano H, Morita T, Iida H, Asada K, Kato M, Uno K, Hirose K, Matsumoto A, Takenaka K, Hirata Y, Eto F, Nagai R, Sato Y, Nakajima T. Hemodynamic and hormonal responses to a short-term low-intensity resistance exercise with the reduction of muscle blood flow. Eur J Appl Physiol 2005; 95: 65-73
    CrossrefPubMedSearch in Google Scholar
  • 43 Takarada Y, Nakamura Y, Aruga S, Onda T, Miyazaki S, Ishii N. Rapid increase in plasma growth hormone after low-intensity resistance exercise with vascular occlusion. J Appl Physiol 2000; 88: 61-65
    PubMedSearch in Google Scholar
  • 44 Tanimoto M, Madarame H, Ishii N. Muscle oxygenation and plasma growth hormone concentration during and after resistance exercise: Comparison between “KAATSU” and other types of regimen. Int J KAATSU Training Res 2005; 1: 51-56
    CrossrefPubMedSearch in Google Scholar