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

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.

Blood flow‐restricted walking in older women: does the acute hormonal response associate with muscle hypertrophy?

“…Furthermore, the increase in noradrenaline and insulin was higher in BFR-walk than in CON-walk. Insulin and noradrenaline appear to activate both phosphatidylinositol 3-kinase (Bolster et al, 2004;Loenneke et al, 2012b) and MAPK (Dash et al, 2003) signalling pathways. Recently, we found that a bout of BFR-walk had a positive effect on the activation of these pathways (Ozaki et al, 2014).…”

Exercise and Blood Flow Restriction

“…Research has demonstrated an increase in the norepinephrine concentration after BFR exercise (60,89), yet during EMS stimulated involuntary contraction with BFR, the increase was substantially less, possibly indicating that norepinephrine secretion depends on centrally mediated voluntary exertion (36). Loenneke et al (57) discussed the hypertrophic role of catecholamines through b2 adrenoceptor signaling-the most prominent adrenoceptor found in skeletal muscle tissue. The binding of catecholamines to b2 adrenoceptors initiates the G--protein--linked activation of the cyclic AMP secondary messenger, and then activation of protein kinase A dependent (e.g., inhibition of calcium--dependent proteolysis) and independent mechanisms (activation of the phosphatidylinositol--3--kinase pathway).…”

ADRB2 (adrenoceptor beta 2, surface)

“…β2 adrenergic receptor is widely distributed, this protein is expressed by airway smooth muscle (30-40000 per cell), epithelial and endothelial cells of the lung, smooth muscle of blood vessels, skeletal muscle, mast cells, lymphocytes, oral and skin keratinocytes and also by diverse cancer cells (Kohm and Sanders, 2001;Lutgendorf et al, 2003;Johnson, 2006;Sood et al, 2006;Thaker et al, 2006;Yang et al, 2006;Sastry et al, 2007;Yu et al, 2007;Liu et al, 2008a;Liu et al, 2008b;Shang et al, 2009;Sivamani et al, 2009;Yang et al, 2009;Bernabé et al, 2011;Bravo-Calderón et al, 2011-2012Steenhuis et al, 2011;Zhang et al, 2011;Loenneke et al, 2012).…”

“…Note Genetic and protein expression of β2 adrenergic receptor was demonstrated in OSCC by using RT-PCR assay, Western blot and immunohistochemistry (Shang et al, 2009;Bernabé et al, 2011;Bravo-Calderón et al, 2011-2012. Investigations performed in different oral cancer cell lines demonstrated that β2 adrenergic receptor signaling by norepinephrine increases cell proliferation and invasion, and upregulates interleukin-6 (IL-6) gene expression and protein release (Shang et al, 2009;Bernabé et al, 2011).…”