Specific Effects of n-3 Fatty Acids and 8-bromo-cGMP on the Cyclic Nucleotide Phosphodiesterase Activity in Neonatal Rat Cardiac Myocytes

The authors have previously resolved four forms of cyclic nucleotide phosphodiesterase (PDE) in neonatal rat cultured cardiomyocytes by use of high-performance liquid chromatography (HPLC) and have shown that the response of the cGMP-stimulated PDE to the effector cGMP was markedly reduced as compared to that of the corresponding isoform present in the heart ventricle of adult rat (70%v350%). When neonatal rat ventricular myocytes were grown in a medium enriched in docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA), an increase of the basal level of cAMP and mainly cGMP was observed. The cGMP-PDE specific activity in the unfractionated cytosol of DHA-, EPA- or 8-bromo-cGMP-enriched cardiomyocytes was lower than that observed in control cells, whereas the cAMP-PDE specific activity remained unchanged whatever the treatment used. At the same time, the response of the cGMP-stimulated PDE to cGMP was substantially increased in n-3 fatty acid-enriched cardiomyocytes and reached the same level as in the whole ventricle (340%). The treatment of neonatal cardiomyocytes with 8-bromo-cGMP also re-established the sensitivity of this cGMP-stimulated isozyme to cGMP (320%). These results suggest a common mechanism for polyunsaturated fatty acids and 8-bromo-cGMP in the regulation of the cGMP-stimulated PDE activity in cardiomyocytes from new-born rats.