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

Abstract

We previously have shown that treatment of neonatal rats (days 1–10) with Nerve Growth Factor (NGF) or its antibody (Ab) modifies α-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 α 1-receptor to the Na K pump. This receptor-effector pathway results in α 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 α-agonist. We now report the effects of administration of NGF, Ab or placebo on β-adrenergic receptor-effector coupling in neonatal rats. Rats were administered NGF, Ab or placebo on days 1–10 of life. On day 10, the β-receptor number and affinity and the stimulatory G-protein, G s, were equivalent across groups. Moreover, the ventricular automatic response to β-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 β-adrenergic receptor-effector coupling considered in light of our prior studies on α-adrenergic coupling suggest that the development of sympathetic innervation is more a determinant of α than β adrenergic modulation of ventricular rhythm.