Thyroid hormone increases rat atrial natriuretic peptide messenger ribonucleic acid accumulation in vivo and in vitro

Thyroid hormone has a number of effects on cardiovascular and renal function which are shared by the atrial natriuretic peptide (ANP). We attempted to demonstrate a relationship between the two by studying the effects of thyroid hormone on the expression of the ANP gene and the secretion of its encoded protein. Thyroid hormone, when given to thyroidectomized rats, increased plasma ANP levels by approximately 2-fold in both watered and dehydrated animals. Cardiac ANP mRNA in dehydrated animals fell to 25% of that in the water-replete controls. T4 increased cardiac ANP mRNA 3-fold in dehydrated animals, but failed to alter ANP mRNA in those animals allowed free access to water. The effect of thyroid hormone appeared to take place, at least in part, at the level of the ANP-synthesizing cardiocyte. T3, at concentrations ranging from 10(-10)-10(-8) M, increased ANP mRNA levels a maximum of 2-fold in primary cultures of neonatal cardiocytes. Both basal and T3-stimulated ANP transcripts appeared to be identical to their counterparts in the adult atria, as assessed by blot hybridization and S1 nuclease analysis. T3 (10(-8) M) also effected a 2-fold increase in media ANP immunoreactivity. These data indicate that thyroid hormone increases the secretion and genetic expression of ANP in vivo and in vitro and suggests a role for the peptide as a mediator of at least some thyroid hormone effects in the cardiovascular system.