The functional cardiac innervation of 61 puppies from nine different litters (2-8 littermates), ranging in age from 1 day to 7 wk, was investigated. The efferent sympathetic nervous system exerted minimal effects on the heart of 1-day-old puppies, gradually influencing the heart more thereafter such that by 7 wk of life it was functionally mature. In contrast, efferent parasympathetic cardiac innervation was well developed at birth, maturing thereafter such that by 4-7 wk of age its capacity to modulate the heart was similar to that found in adults. The right- and left-sided efferent sympathetic and parasympathetic intrathoracic nervous systems induced similar cardiac modulation throughout this period of development. Cardiac myocyte beta-adrenergic receptors were partially functional at birth, as determined by responses elicited by supramaximal doses of the beta-agonist isoproterenol. Responses elicited by isoproterenol became greater over the following 7 wk of life, when they were found to be similar to those elicited in adults. By 1 wk of age, synaptic mechanisms in intrathoracic sympathetic ganglia involved in cardiac regulation were relatively well developed, with cardiopulmonary-cardiac reflexes present but not functionally mature at that age. It is concluded that maturation of the efferent sympathetic nervous system modulating the canine heart depends to a large extent on the ontogeny of cardiac beta-adrenergic receptors rather than the ontogeny of synapses in intrathoracic ganglia. Furthermore, even though functional cardiac efferent parasympathetic innervation is present before efferent sympathetic innervation, both reach maturity at about the same age.
The beta adrenergic receptor antagonist propranolol alters mitogenic and apoptotic signaling in late stage breast cancer
