NEUROPEPTIDE-Y STIMULATES HYPERTROPHY OF ADULT VENTRICULAR CARDIOMYOCYTES

It was investigated whether neuropeptide Y (NPY) could exert a trophic effect on ventricular myocytes isolated from the adult rat heart. Two different culture models were used: day 1 and 7 cultures of cardiomyo cytes. In day 1 and 7 cultures, NPY caused an increase in cellular pro tein mass. In day 1 cultures, NPY (10 nM) increased the protein-to-DNA ratio within 24 h by 10.1+/-2.8% (P < 0.01), but did not stimulate th e incorporation of [C-14]phenylalanine into cell proteins. The degrada tion of proteins was retarded in presence of NPY, revealed by pulse-ch ase experiments. In day 7 cultures, NPY (10 nM) increased the protein- to-DNA ratio within 24 h by 33.9+/-5.0% (P < 0.01), increased the RNA- to-DNA ratio by 19.2+/-6.4%, and stimulated the incorporation of [C-14 ]phenylalanine by 45.5+/-4.5% (P < 0.01). As in day 1 cultures, protei n degradation was retarded. The specific activities of cytosolic creat ine kinase and lactate dehydrogenase were increased in presence of NPY . This study demonstrates for the first time that NPY is a trophic fac tor for cardiomyocytes. NPY can cause an increase in cellular mass of protein, i.e., hypertrophy, by two mechanisms: 1) reduction of degrada tion of protein, found in day 1 and 7 cultures, and 2) stimulation of protein synthesis, observed only in day 7 cultures. The responsiveness of protein synthesis to NPY stimulation is induced during prolonged i ncubation in culture.