DNA dependent RNA polymerase activity of rat heart nuclei during experimentally induced hypertrophy.

Nuclei from groups of twelve pooled left ventricles of rats were isolated and DNA, RNA and protein contents of the nuclear suspension were determined. RNA polymerase activity was assayed in the presence of either Mg++ or Mn++ and (NH4)2SO4. Electronmicroscopic examination of normal nuclear preparations revealed undamaged nuclei with very little contamination. Cardiac enlargement was produced by constricting the abdominal aorta in experimental animals. The operated animals were sacrificed at different intervals after operation between 4 hours and two weeks The "pure" nuclear suspensions of the myocardium of these animals was isolated for examination. Sham operated animals were used as control up till the third day, after this time normal animal served as control, since the difference between sham operated and normal animal did not persist beyond 3 days. An increase in RNA, DNA and protein content of the nuclear preparation was observed in aortic constricted animals. DNA showed a delayed increase compared to the time course of changes in RNA and protein. RNA polymerase activity showed a biphasic increase following constriction in both Mg ++ and Mn++-(NH4)2SO4 activated systems. In rats killed soon after constriction (4 hours in this study) the Mn++-(NH4)2SO4 system showed the greater percentage increase and on the 3rd-4th day after aortic constriction the increase was considerably greater in the Mg ++ activated system. An increase in RNA polymerase activity as early as 4 hours after aortic constriction was demonstrated in this study, among other findings. This early increase suggests that the stimulation of RNA synthesis - one of the first biochemical events in hypertrophy may play a role in translating the mechanical stress caused by increased outflow resistance into tissue growth