Neuropeptide Y modifies the hypertrophic response of adult ventricular cardiomyocytes to norepinephrine

Abstract

Objective: The hypertrophic response of adult rat cardiomyocytes to norepinephrine via α-adrenoceptor stimulation is limited by an inhibitory cross-talk of simultaneously β-adrenoceptor stimulation. On the other hand, neuropeptide Y (NPY), known to be co-secreted with norepinephrine from intramural nerve endings of the heart, exerts an anti-β-adrenergic effect. Therefore, it should be expected that NPY enhances the hypertrophic response to norepinephrine. This hypothesis was addressed in the present study. Methods: Isolated adult ventricular cardiomyocytes from rats were used. As parameters of hypertrophic growth we investigated cell volume, cross-sectional area, protein mass. Protein and RNA synthesis were determined by incorporation of [¹⁴C]phenylalanine or [¹⁴C]uridine, respectively. Results: Norepinephrine (1 μmol/l) did not significantly increase protein or RNA synthesis. In co-presence of NPY (100 nmol/l), however, norepinephrine increased protein synthesis by 44% and RNA synthesis by 18%. Under the same conditions, NPY enhanced the effect of norepinephrine on cell volume from +6.4 to +18.2%, its effect on cross-sectional area from +16 to +23%, and increased the protein/DNA ratio from 32.5 to 35.6 mg/mg. In parallel, norepinephrine caused a translocation of PKC-α and PKC-δ into the particular fractions and this effect of norepinephrine was also enhanced by co-presence of NPY. In contrast, NPY did not enhance ERK-activation caused by norepinephrine. Conclusion: Our study indicates the anti-β-adrenergic effect of NPY is sufficient to modulate the hypertrophic response of adult ventricular cardiomyocytes to norepinephrine. The results suggest that the hypertrophic effect of norepinephrine via α-adrenoceptor stimulation can be modulated by co-release of NPY from intramural nerve endings.

Adrenergic (ant)agonists, Hypertrophy, Myocytes, Neurotransmitters, Signal transduction