Modification of subcellular organelles in pressure-overloaded heart by etomoxir, a carnitine palmitoyltransferase I inhibitor.
To examine the signals regulating cardiac growth and molecular structure of subcellular organelles, cardiac hypertrophy was induced in rats by constriction of the abdominal aorta for 12-13 wk or by treatment with a carnitine palmitoyltransferase I inhibitor, etomoxir (12-15 mg/kg body wt) for 12-13 wk. In contrast to pressure overload, etomoxir redistributed the myosin isozyme population from V3 to V1 and increased the sarcoplasmic reticulum (SR) Ca(2+)-stimulated ATPase activity. When rats with pressure-overloaded hearts were treated with etomoxir, the cardiac hypertrophy was increased whereas the shift in myosin isozymes from V1 to V3 was prevented and the depression in SR Ca(2+)-stimulated ATPase activity was reversed. Plasma thyroid hormone and insulin concentrations were not altered but triglyceride concentrations were reduced in etomoxir-treated rats with pressure overload. The data demonstrate a dissociation between cardiac muscle growth and changes in subcellular organelles and indicate that a shift in myocardial substrate utilization may represent an important signal for molecular remodeling of the heart.
Rupp
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Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Canada.
Elimban
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V
Dhalla
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NS
D000818:Animals; D001012:Aorta, Abdominal; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure; D006332:Cardiomegaly / Q000139:chemically induced; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors*; D003250:Constriction; D004798:Enzymes / Q000032:analysis / Q000187:drug effects; D004852:Epoxy Compounds / Q000494:pharmacology*; D006352:Heart Ventricles / Q000187:drug effects / Q000254:growth & development / Q000473:pathology*; D006728:Hormones / Q000097:blood; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D015388:Organelles / Q000187:drug effects / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D004798:Enzymes; D004852:Epoxy Compounds; D006728:Hormones; D007004:Hypoglycemic Agents; D014280:Triglycerides; D002334:Carnitine O-Palmitoyltransferase; C054207:etomoxir