Differential influence of fasting and BM13.907 treatment on growth and phenotype of pressure overloaded rat heart.
To examine metabolic influences on markers of the fetal phenotype of pressure overloaded rat heart, rats with stenosis of the abdominal aorta were intermittently fasted for 10-12 weeks. Although intermittent fasting, which reduces insulin mediated glucose uptake in the heart and moderate pressure overload of the left ventricle increased the proportion of myosin beta-heavy chains (beta-MHC) and reduced the Ca(2+)-stimulated ATPase activity of sarcoplasmic reticulum (SR) to a similar extent, these interventions had no additive effects when combined. Furthermore, addition of sucrose (0.8%) to the drinking water prevented the changes in both the beta-MHC proportion and SR Ca(2+)-stimulated ATPase activity due to pressure overload or fasting. To assess the effects of a drug which stimulates glucose-carrier translocation, rats with stenosis of the abdominal aorta were treated with BM13.907 (50 and 100 mg/kg daily for 10-12 weeks). This treatment amplified the left ventricular hypertrophy (+43 vs. 21% of untreated rats) and increased the beta-MHC proportion. The SR Ca(2+)-stimulated ATPase activity of pressure overloaded rats treated with BM13.907 (100 mg/kg/day) was, however, not reduced compared with sham operated control rats. Thus, an intervention which is known to stimulate insulin-mediated glucose-carrier translocation, but not glucose-carrier activation, partially prevented the characteristic phenotype of pressure overloaded hearts. These data provide further evidence in favor of metabolic influences linked to glucose uptake on growth and phenotype of the pressure overloaded heart.
Rupp
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H
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Canada.
Elimban
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V
Dhalla
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NS
D000284:Administration, Oral; D000480:Alkynes / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001012:Aorta, Abdominal; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*; D003251:Constriction, Pathologic; D005215:Fasting / Q000502:physiology*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley
D000480:Alkynes; C116909:BM 13.907; D007004:Hypoglycemic Agents