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

ANG II mediates the hypertrophic response of overloaded cardiac muscle, lik ely via the ANG II type 1 (AT(1)) receptor. To examine the potential role o f 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 gastrocnemi us muscle (experiment 1) or both the gastrocnemius and plantaris muscles (e xperiment 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 so leus muscle hypertrophy by 57 and 96%, respectively (as measured by total m uscle 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 os motic pump) rescued the lost hypertrophic response in ACE-inhibited animals by 71%. Furthermore, orally administering an AT(1) receptor antagonist ins tead of an ACE inhibitor produced a 48% attenuation of overload-induced hyp ertrophy 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.