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 p ressure overloaded rat heart, rats with stenosis of the abdominal aort a were intermittently fasted for 10-12 weeks. Although intermittent fa sting, which reduces insulin mediated glucose uptake in the heart and moderate pressure overload of the left ventricle increased the proport ion of myosin beta-heavy chains (beta-MHC) and reduced the Ca2+-stimul ated ATPase activity of sarcoplasmic reticulum (SR) to a similar exten t, these interventions had no additive effects when combined. Furtherm ore, addition of sucrose (0.8%) to the drinking water prevented the ch anges in both the beta-MHC proportion and SR Ca2+-stimulated ATPase ac tivity due to pressure overload or fasting. To assess the effects of a drug which stimulates glucose-carrier translocation, rats with stenos is 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-MH C proportion. The SR Ca2+-stimulated ATPase activity of pressure overl oaded rats treated with BM13.907 (100 mg/kg/day) was, however, not red uced compared with sham operated control rats. Thus, an intervention w hich is known to stimulate insulin-mediated glucose-carrier translocat ion, but not glucose-carrier activation, partially prevented the chara cteristic phenotype of pressure overloaded hearts. These data provide further evidence in favor of metabolic influences linked to glucose up take on growth and phenotype of the pressure overloaded heart.