Severe food restriction induces myocardial dysfunction related to SERCA2 activity

Previous studies have shown that food restriction promotes myocardial dysfunction in rats. However, the molecular mechanisms that are responsible are unclear. We investigated the role of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) on myocardial performance in food-restricted rats. Male Wistar-Kyoto rats, 60 days old, were fed a control or restricted diet (daily energy intake reduced to 50% of the control) for 90 days. Expression of Serca2a, phospholamban (PLB), Na(+)/Ca(2+) exchanger (NCX), and thyroid hormone receptor (TR alpha 1, TR beta 1) mRNA was determined by quantitative PCR. SERCA2 activity was measured by using 20 mu mol/L cyclopiazonic acid (CPA) in a left ventricular papillary muscle preparation during isometric contraction in basal conditions and during post-rest contraction. Serum concentrations of thyroxine (T(4)) and thyrotropin (TSH) were also determined. The 50%-restricted diet reduced body and ventricular weight and serum T4 and TSH levels. The interaction of CPA and food restriction reduced peak developed tension and maximum rate of tension decline (-dT/dt), but increased the resting tension intensity response during post-rest contraction. PLB and NCX mRNA were upregulated and TR alpha 1 mRNA was downregulated by food restriction. These results suggest that food restriction promotes myocardial dysfunction related to impairment of sarcoplasmic reticulum Ca(2+) uptake as a result of a hypothyroid state.