Ribonucleic acid synthesis in experimental cardiac hypertrophy in rats. II. Aspects of regulation.

The sequence of events which lead to increased RNA synthesis in the heart following aortic constriction was studied with the use of inhibitors of protein and RNA synthesis. Puromycin given during the first 4 hours after operation inhibited the increase in RNA labeling with [32P] H3PO4 that occurred after 4 hours of aortic constriction without inhibiting RNA labeling in sham-operated rats. Puromycin had no effect on the 32P labeling of the alpha-phosphate of AMP which suggests that the effect on labeling of RNA is not mediated by the lowering of precursor specific activity. The dose of puromycin used inhibited the labeling of heart muscle protein with 3H leucine. Parafluorophenylalanine had no selective inhibitory effect on the increase of RNA labeling in the hypertrophying heart. The most likely interpretation of these data is that, following aortic constriction, synthesis of protein is required for subsequent stimulation of RNA synthesis, and this protein may be dependent upon the synthesis of new RNA templates. Any early increased synthesis would be of a minority species of protein since there was no increase in amino acid labeling of total heart protein until 4 to 6 hours after aortic constriction. The stimulation of RNA labeling by aortic constriction was unaffected by digitalis treatment. The pressure-time index did not correlate with the increased labeling of RNA.