Thyroid hormone stimulates Na, K-ATPase gene expression in the hemodynamically unloaded heterotopically transplanted rat heart

Regulation of myocardial Na, K-ATPase gene expression by thyroid hormone wa s investigated in the heterotopically transplanted rat heart to distinguish the direct effects of the hormone on the heart from effects secondary to i ncreased hemodynamic workload. In this model, the transplanted heart is his tologically normal and spontaneously beating, but hemodynamically unloaded. Three days after transplantation, relative contents of ventricular Na, K-A TPase alpha(2)- and beta(1)-mRNAs and alpha(1)- and alpha(2)-proteins were increased twofold to threefold in the transplanted heart, but these changes were transient. We next determined the maximal triiodothyronine (T-3)-indu ced changes that are observed in various parameters of Na, K-ATPase express ion in the heart: treatment of nontransplanted euthyroid rats with T-3 to r each hyperthyroid steady state resulted in significant increases in heart w eight, RNA and RNA/protein ratio, Na, K-ATPase activity, Na, K-ATPase alpha (2)-protein and enzyme activity, and approximately threefold increase in bo th alpha(2)- and beta(1)-mRNA content. The effect of treatment with thyroxi ne (T-4) On the heterotopically transplanted and the in situ heart was then examined. T-4 treatment (of the host) resulted in a significant increase i n Na, K-ATPase alpha(1)-, alpha(2)-, and beta(1)-mRNAs in transplanted hear ts (1.6 +/- 0.1-, 2.4 +/- 0.2-, and 1.7 +/- 0.1-fold, respectively), that w as associated with a 2.2 +/- 0.2-fold increase in alpha(2) protein as compa red to transplanted hearts in diluent-treated euthyroid hosts (p < 0.05 for all changes). In addition, T-4-induced increments in transplanted hearts w ere similar to those observed in the corresponding in situ hearts of host r ats treated with T-4. We conclude that the increase in Na, K-ATPase express ion by thyroid hormone largely occurs independently of increased cardiac wo rk elicited by the hormone and reflects a direct action of the hormone on N a, K-ATPase gene expression.