ANG II is required for optimal overload-induced skeletal muscle hypertrophy

Abstract

ANG II mediates the hypertrophic response of overloaded cardiac muscle, likely via the ANG II type 1 (AT(1)) receptor. To examine the potential role of ANG II in overload-induced skeletal muscle hypertrophy, plantaris and/or soleus muscle overload was produced in female Sprague-Dawley rats (225-250 g) by the bilateral surgical ablation of either the synergistic gastrocnemius muscle (experiment 1) or both the gastrocnemius and plantaris muscles (experiment 2). In experiment 1 (n = 10/group), inhibiting endogenous ANG II production by oral administration of an angiotensin-converting enzyme (ACE) inhibitor during a 28-day overloading protocol attenuated plantaris and soleus muscle hypertrophy by 57 and 96%, respectively (as measured by total muscle protein content). ACE inhibition had no effect on nonoverloaded (sham-operated) muscles. With the use of new animals (experiment 2; n = 8/group), locally perfusing overloaded soleus muscles with exogenous ANG II (via osmotic pump) rescued the lost hypertrophic response in ACE-inhibited animals by 71%. Furthermore, orally administering an AT(1) receptor antagonist instead of an ACE inhibitor produced a 48% attenuation of overload-induced hypertrophy that could not be rescued by ANG II perfusion. Thus ANG II may be necessary for optimal overload-induced skeletal muscle hypertrophy, acting at least in part via an AT(1) receptor-dependent pathway.

Characterization of angiotensin-converting enzymes 1 and 2 in the soleus and plantaris muscles of rats

“…Previous data regarding the role of Ang II in the control of skeletal muscle mass are controversial. Ang II has been shown to promote muscle atrophy (15); nevertheless, other studies have reported that Ang II induces skeletal muscle hypertrophy associated with strength gain (16,17).…”

Genes and the ageing muscle: a review on genetic association studies

“…The primary role of ACE in the renin-angiotensin system is to convert angiotensin I into angiotensin II (Rigat et al 1990), which not only acts as a vasoconstrictor but also regulates smooth (Berk et al 1989;Geisterfer et al 1988) and cardiac muscle growth (Sadoshima et al 1993;Ishigai et al 1997). ACE inhibitors have been shown to inhibit hypertrophy in overloaded muscle, which also suggests a role for angiotensin II in skeletal muscle hypertrophy (Gordon et al 2001;Westerkamp and Gordon 2005).…”

Differential response to resistance training in CHF according to ACE genotype

“…Angiotensin II is a mediator of the hypertrophic response to mechanical loading in rodent muscle (28,29) . The potential synergistic actions of angiotensin II in combination with mechanical loading provides a mechanism by which the previously observed (16,17) greater increases in strength following resistance training in subjects with the D allele may have occurred.…”