[Modelling of myocardial hypertrophy in vitro for solving problems of medicinal correction]

The work has been done on primary heart culture from neonatal rat ventricle. Cardiomyocyte hypertrophy was modelled using noradrenaline (NA), angiotensin II (AII) and fetal serum, respectively. Cell hypertrophy of primary heart cultures was assessed by measuring the surface area, the scope of protein synthesis estimated by 3H-leucine autoradiography and the contents of nucleic acids in gallocyanin-chromalum stained cardiomyocytes. The structure of myofibrillar apparatus was studied by rhodamine-conjugated phalloidin and indirect immunofluorescence of muscle alpha-actinin. Treatment with 10(-6) M NA increased 3H-leucine incorporation in 9-day old heart culture by 42% without changing cell size. AII in a dose 1 microM stimulated protein synthesis activity by 1.3 fold and the surface area by 1.7 fold, both in 2- and 9-day old primary heart cultures. The maximum stimulation of cell hypertrophy was provided by the medium supplemented with fetal serum. RNA contents in the cytoplasm of cardiomyocytes increased by 7.8 fold and the myocardial cell size by 2.9 fold in serum-supplemented culture by 9 days of cultivation. In the medium with fetal serum, amounts of cardiomyocytes with tetraploid nuclei reached 33%, against 14% in control. Coculturing of myocardiocytes and fibroblasts rendered effects of fetal serum on the growth of myocardiocytes. Cultivation in the presence of 1 microM enalapril, an ACE inhibitor, suppressed the development of cardiac muscle cells hypertrophy. The effect of enalapril depended on the degree of cellular hypertrophy. Addition of 10 microM amiloride to the medium lowered the protein synthesis by 29% independently on the initial cellular hypertrophy.