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Research ArticleArticle

Impaired Skeletal Muscle Performance in the Early Stage of Cardiac Pressure Overload in Rabbits: Beneficial Effects of Angiotensin-Converting Enzyme Inhibition

Catherine Coirault, Olivier Langeron, Francine Lambert, François-Xavier Blanc, Guy Lerebours, Nancy Claude, Bruno Riou, Denis Chemla and Yves Lecarpentier
Journal of Pharmacology and Experimental Therapeutics October 1999, 291 (1) 70-75;
Catherine Coirault
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Olivier Langeron
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Francine Lambert
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François-Xavier Blanc
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Guy Lerebours
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Nancy Claude
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Bruno Riou
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Denis Chemla
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Yves Lecarpentier
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Abstract

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 designed to assess whether skeletal muscle dysfunction develops in the early stage of cardiac overload and if so, whether such functional alterations can be prevented by ACE inhibition. Mechanical performance, cross-bridge (CB) properties, and myosin heavy chain composition were investigated in respiratory and limb skeletal muscles of rabbits with moderate cardiac hypertrophy, and after single therapy with the ACE inhibitor perindopril (PE). After constriction of the aorta, the rabbits were treated during a 10-week period with either PE (1 mg/kg/day; n = 9) or a placebo (PL; n = 15). A third group of sham-operated animals received PL (n = 10). Analyses were performed on isolated diaphragm and soleus strips. Compared with sham-operated animals (shams), 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 maximum shortening velocity between PE and shams. In both muscles, the total number of CBs was significantly lower in PL than in shams, but did not differ 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 diaphragm and soleus muscles was affected early in the development of chronic pressure overload. Single therapy with PE tended to preserve muscle strength, essentially by limiting the loss of CBs.

Footnotes

  • Send reprint requests to: Dr. C. Coirault, Institut National de la Santé et de la Recherche Médicale U451-LOA-Ecole Polytechnique, Batterie de l’Yvette, 91761 Palaiseau Cedex, France. E-mail: coirault{at}enstay.ensta.fr

  • ↵1 This work was supported in part by Servier Laboratories, Institut de Recherche International Servier Courbevoie, France.

  • Abbreviations:
    ACE
    angiotensin-converting enzyme
    PL
    placebo
    PE
    perindopril
    Lo
    optimal initial muscle length
    Po
    maximum isometric tension
    CB
    cross-bridge
    CHF
    congestive heart failure
    MHC
    myosin heavy chain
    • Received March 8, 1999.
    • Accepted June 2, 1999.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 291 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 291, Issue 1
1 Oct 1999
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Research ArticleArticle

Impaired Skeletal Muscle Performance in the Early Stage of Cardiac Pressure Overload in Rabbits: Beneficial Effects of Angiotensin-Converting Enzyme Inhibition

Catherine Coirault, Olivier Langeron, Francine Lambert, François-Xavier Blanc, Guy Lerebours, Nancy Claude, Bruno Riou, Denis Chemla and Yves Lecarpentier
Journal of Pharmacology and Experimental Therapeutics October 1, 1999, 291 (1) 70-75;

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Research ArticleArticle

Impaired Skeletal Muscle Performance in the Early Stage of Cardiac Pressure Overload in Rabbits: Beneficial Effects of Angiotensin-Converting Enzyme Inhibition

Catherine Coirault, Olivier Langeron, Francine Lambert, François-Xavier Blanc, Guy Lerebours, Nancy Claude, Bruno Riou, Denis Chemla and Yves Lecarpentier
Journal of Pharmacology and Experimental Therapeutics October 1, 1999, 291 (1) 70-75;
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