Pyrimidine nucleotide metabolism in cardiac hypertrophy.

Abstract

Cardiac hypertrophy was induced in rats either by isoprenaline treatment or by experimental abdominal aortic stenosis. In both models, the UTP content increased in the hypertrophying heart, while the ATP level remained depressed. The rate of net synthesis of uracil nucleotides, estimated by phosphate incorporation into alpha-phosphate groups, was largely increased during the first stage of hypertrophy (X 3.6 and 2.6, respectively). At identical stages of hypertrophy, the rate of synthesis of ribosomal RNA, measured after continuous intracardiac infusion of 3H-uridine, was increased by 1.6 and 2.5 times. A comparison of the changes in time course of the levels of UTP and RNA and their turnover suggests that the metabolism of uracil nucleotides and that of ribosomal RNA are closely interrelated. The increase in the rate of synthesis of pyrimidine is interpreted as an adaptational change in nucleotide metabolism in response to the increased requirement of precursors for RNA synthesis. The possible limiting role of pyrimidine nucleotides in the hypertrophic process is discussed.