Beta adrenergic modulation of cardiac rhythm in a rat model of altered sympathetic neural development

We previously have shown that treatment of neonatal rats (days 1-10) with Nerve Growth Factor (NGF) or its antibody (Ab) modifies alpha-adrenergic receptor-effector coupling, such that innervated hearts at day 10 show high levels of a 41 kDa GTP regulatory protein (G protein) that is a substrate for pertussis toxin and that links the alpha 1-receptor to the Na/K pump. This receptor-effector pathway results in alpha adrenergic-induced decreases in automaticity. In contrast, non-innervated hearts at day 10 show lower levels of the pertussis toxin sensitive G-protein and increases in automaticity induced by alpha-agonist. We now report the effects of administration of NGF, Ab or placebo on beta-adrenergic receptor-effector coupling in neonatal rats. Rats were administered NGF, Ab or placebo on days 1-10 of life. On day 10, the beta-receptor number and affinity and the stimulatory G-protein, Gs, were equivalent across groups. Moreover, the ventricular automatic response to beta-adrenergic receptor stimulation was equivalent across groups suggesting there was no change in receptor-effector coupling as a result of the difference in innervation. These results on beta-adrenergic receptor-effector coupling considered in light of our prior studies on alpha-adrenergic coupling suggest that the development of sympathetic innervation is more a determinant of alpha than beta adrenergic modulation of ventricular rhythm.