Impaired skeletal muscle performance in the early stage of cardiac pressure overload in rabbits: Beneficial effects of angiotensin-converting enzyme inhibition

Abnormalities of skeletal muscles are frequently observed in patients with congestive heart failure. In these patients, angiotensin-converting enzyme (ACE) inhibitors improve exercise performance. The present study was design ed to assess whether skeletal muscle dysfunction develops in the early stag e of cardiac overload and if so, whether such functional alterations can be prevented by ACE inhibition. Mechanical performance, cross-bridge (CB) pro perties, and myosin heavy chain composition were investigated in respirator y and limb skeletal muscles of rabbits with moderate cardiac hypertrophy, a nd after single therapy with the ACE inhibitor perindopril (PE). After cons triction of the aorta, the rabbits were treated during a 10-week period wit h either PE (1 mg/kg/day; n = 9) or a placebo (PL; n = 15). A third group o f sham-operated animals received PL (n = 10). Analyses were performed on is olated diaphragm and soleus strips. Compared with sham-operated animals (sh ams), peak tetanic tension in PL fell by 40% in diaphragm and 34% in soleus . There were no significant differences in peak tetanic tension and the max imum shortening velocity between PE and shams. In both muscles, the total n umber of CBs was significantly lower in PL than in shams, but did not diffe r between shams and PE. The elementary force per CB did not differ between groups. In both muscles, the myosin heavy chain composition did not differ between groups. The study demonstrated that intrinsic performance of diaphr agm and soleus muscles was affected early in the development of chronic pre ssure overload. Single therapy with PE tended to preserve muscle strength, essentially by limiting the loss of CBs.