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.
Steinberg
S F
SF
Department of Pharmacology, Columbia University College of Physicians and Surgeons, New York, NY 10032.
Rosen
T S
TS
Malfatto
G
G
Rosen
M R
MR
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000378:metabolism; D006321:Heart / Q000254:growth & development / Q000294:innervation / Q000502:physiology*; D006339:Heart Rate / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000254:growth & development / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D019204:GTP-Binding Proteins; D007545:Isoproterenol