Sympathetic Nervous System Neuroplasticity

Abstract

In human and experimental models of heart failure there is widespread change in the sympathetic nervous system. This involves preferential activation of the sympathetic nervous outflow to the heart, impairment of norepinephrine reuptake by sympathetic nerves, and reduction of the content of norepinephrine in the failing myocardium, attributable in part to sympathetic neuronal rarefaction.1–4 Michael Kreusser and colleagues from the University of Heidelberg, in their article in this issue of Hypertension ,5 report rapid correction of 2 of these abnormalities— reduced norepinephrine reuptake and depleted cardiac norepinephrine stores—in the rat heart failure model they studied, following injection of a single dose of the neurotrophin, nerve growth factor (NGF), into the left stellate ganglion. The neurotrophins are regulators of neural survival, development, and function that have a key role in vertebrate embryonic life but are increasingly documented to have important influences also in maturity.6,7 The article by Kreusser et al5 underscores the extraordinary neuroplasticity of the sympathetic nervous system in adulthood, a structural and functional neuronal ebb and flow that is orchestrated in large part by NGF. Perhaps the most explicit example of human sympathetic neuroplasticity is the regrowth and remodeling of the sympathetic nerves of the heart following cardiac transplantation. With the exception of the sympathetic nerves to the recipient atria, which depending on the surgical technique may be left intact, all cardiac sympathetic nerves are cut at the time of surgical removal of the failing heart. Subsequently, over several years, sympathetic fiber ingrowth leads to substantial reinnervation of …