CHRONIC EXPOSURE TO NEUROPEPTIDE-Y DETERMINES CARDIAC ALPHA-1-ADRENERGIC RESPONSIVENESS

The onset of sympathetic innervation induces a developmental change in the cardiac alpha-1-adrenergic chronotropic response from an increase to a decrease in rate. The mechanism by which innervation induces this alteration is unknown. Neuropeptide Y (NPY), which is found abundantly in cardiac sympathetic nerve terminals, was considered as a possible mediator for this effect. Chronic conditioning by NPY in noninnervated myocyte cultures stimulated the effect of sympathetic innervation in inducing the alpha-1-inhibitory chronotropic response. Chronic conditioning by the NPY antagonist PYX-2 blocked the effect of innervation. Thus endogenous NPY may modulate alpha-1-adrenergic responsiveness during the ontogeny of cardiac sympathetic innervation.