Recovery of chronotropic responsiveness after systemic 6-hydroxydopamine treatment: studies in the pithed rat

In pithed rats, neurally mediated chronotropic responses to thoracolumbar stimulation were reduced substantially 1 day after animals were treated with the neurotoxin 6-hydroxydopamine (6-HDA), which produced a subtotal destruction of postganglionic sympathetic nerve terminals. However, the chronotropic responses of 6-HDA-treated rats recovered to near normal within 1 week despite 90% depletion of cardiac norepinephrine (NE). This recovery of function appeared to depend upon function in surviving sympathetic nerves, and was associated with increased synthesis and release of NE from those neurons as well as diminished inactivation of NE. The gradual development of post-junctional changes, most notably an increase in the density of myocardial beta adrenergic receptors, resulted in enhanced sensitivity to NE and contributed to cardiac function 3 weeks after 6-HDA treatment. In addition, the adrenal medulla increased its synthesis of catecholamines after 6-HDA treatment and thereby contributed to cardiac function, which was especially evident during prolonged sympathoadrenal stimulation. Some of these same adaptations have been observed when rats are subjected to chronic stress, and thus common mechanisms of neuroplasticity may mediate the sympathoadrenal responses to stress and to subtotal injury.