Development of the linkage of beta-adrenergic receptors to cardiac hypertrophy and heart rate control: neonatal sympathectomy with 6-hydroxydopamine.
Presynaptic neural projections are thought to participate in the maturation of postsynaptic sensitivity to neurotransmitters. In the current study, we have examined the effects of sympathectomy with 6-hydroxydopamine on the ontogeny of the linkage of beta-adrenergic receptors to cardiac growth and heart rate control in the rat. Destruction of sympathetic projections at birth compromised the ability of beta-receptor stimulation to evoke cardiac hypertrophy, a defect which persisted into young adulthood. The chronotropic response to beta-receptor activation, assessed by acute challenge with a submaximally-effective dose of isoproterenol, also exhibited a slowed development, but did eventually achieve normal sensitivity. In contrast, neonatal sympathectomy had only minor effects on resting heart rate, basal heart rate (the intrinsic rate in the absence of autonomic input) or maximal heart rate; these animals also showed beta-receptor desensitization of chronotropic action in response to chronic isoproterenol treatment. Chronic isoproterenol treatment itself lowered the basal heart rate, regardless of whether animals were normal or sympathectomized. Thus, during critical developmental periods, sympathetic input to beta-receptors selectively programmes the linkage between postsynaptic receptors, tissue growth and heart rate.
Hou
Q C
QC
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
Seidler
F J
FJ
Slotkin
T A
TA
D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly / Q000209:etiology*; D006339:Heart Rate / Q000187:drug effects*; D006892:Hydroxydopamines; D007545:Isoproterenol / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000502:physiology*; D013563:Sympathectomy, Chemical
D006892:Hydroxydopamines; D011941:Receptors, Adrenergic; D016627:Oxidopamine; D007545:Isoproterenol