A physiological dose of triiodothyronine normalizes cardiac myosin adenosine triphosphatase activity and changes myosin isoenzyme distribution in semistarved rats

Abstract

The possibility that the lowering of thyroid hormone levels which occurs in the nonthyroidal illness syndrome results in a hypothyroid state at the cardiac tissue level was examined in semistarved rats. Rats were fed 50% of their normal food intake in the form of a regular diet (R. diet) or low carbohydrate diet (L.C. diet) for 8 weeks. Animals semistarved for 8 weeks on the R. diet lost 42% of their body weight, while plasma T3 and T4 levels decreased by 45-50%. Semistarvation on the L.C. diet resulted in a 19% weight loss and a similar 46-49% decrease in plasma T3 and T4 levels. Ca++-activated myosin ATPase activity declined by 28% and 48% with the R. and L.C. diets, respectively [normal rats myosin ATPase, 1.30 +/- 0.18 mumol Pi/(mg protein . min) (mean +/- SD); semistarvation R diet, 0.93 +/- 0.15; semistarvation L.C. diet, 0.67 +/- 0.15]. The administration of physiological amounts of T3 (0.3 micrograms T3/100 g BW daily) restored the cardiac myosin ATPase activity in both groups. To confirm that the T3 effect was due to a normalization of the thyroid status at the tissue level, hypothyroid animals on a normal diet were injected with 0.3 micrograms T3 for 4 weeks, which resulted in normalization of myosin ATPase activity levels. Thyroidectomized rats receiving daily T3 injections, and when placed on a 50% reduction of food intake for 4 weeks still maintained normal myosin ATPase activity even though they lost 36% of their body weight. Distribution of cardiac myosin isoenzymes was determined by pyrophosphate polyacrylamide gel electrophoresis. In normal cardiac ventricles, myosin isoenzyme V1 predominates and represents 68 +/- 7% (+/- SD) of the total myosin. Semistarvation resulted in a redistribution of myosin isoenzymes so that V3 myosin was the predominant species (53 +/- 3% of the total myosin). The administration of 0.3 microgram T3/100 g BW daily for 4 weeks to semistarved rats reverted myosin isoenzyme distribution to V1 predominance (V1 myosin, 54 +/- 3% of the total myosin). These results indicate that the semistarvation-induced lowering plasma T3 and T4 levels is an important determinant of myosin ATPase activity and myosin isoenzyme distribution. Restoration of myosin ATPase activity to its normal level and return to myosin V1 predominance after T3 administration make it likely that these changes are related to the lowering of thyroid hormone levels.