Comparative Changes in the ³²P Labeling of Adenine and Uracil Nucleotides in the Hypertrophying Rat Heart

Abstract

The turnover of cardiac adenine and uracil nucleotides was studied in the hypertrophying rat heart by means of the kinetics of incorporation of labeled phosphate into the α-phosphate groups of nucleotides. Cardiac hypertrophy was induced either by chronic isoproterenol treatment (5 mg-kg^-1 body wt. daily, s.c.) or by abdominal aortic constriction. In both experimental models, although the labeling of α-P groups of adenine nucleotides was at first unmodified, the incorporation of [³²P]Phosphate into uracil nucleotides was accelerated early and the stimulation maintained for several days. The intramyocardial concentration of UTP and uracil nucleotides rose during the early phase of hypertrophy, while the ATP and adenine nucleotide pools were depleted. All of these alterations were more pronounced in isoproterenol-treated animals than in those with aortic stenosis. In this experimental model (isoproterenol treatment), the hypertrophy develops faster and is accompanied by a larger increase in cardiac RNA concentration. Thus, the increase in the rate of synthesis of uracil nucleotides may be interpreted as an adaptative change of nucleotide metabolism in response to an increased requirement of precursors for RNA synthesis. The possible limiting role of pyrimidine nucleotides in the hypertrophic process is discussed.