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1 Experimental Cardiology Laboratory, Baker Heart Research Institute, Melbourne, Victoria, Australia
2 Human Neurotransmitter Laboratory, Baker Heart Reseach Institute, Melbourne, Victoria, Australia
3 Wynn Department of Metabolic Cardiology, Baker Heart Reseach Institute, Melbourne, Victoria, Australia
4 Department of Physiology, Monash University, Melbourne, Victoria, Australia
* To whom correspondence should be addressed. E-mail: david.kaye{at}baker.edu.au.
Cardiac-specific overexpression of nerve growth factor (NGF), a neurotrophin, leads to sympathetic hyperinnervation of the heart. As a consequence, adverse functional changes following chronically enhanced sympathoadrenergic stimulation of the heart might develop in this model. However, NGF also facilitates synaptic transmission and norepinephrine uptake, effects that would be expected to restrain such deleterious outcomes. To test this we examined 5-6 month old transgenic (TG) mice overexpressing NGF in the heart and their wild-type (WT) littermates using echocardiography, invasive catheterization, histology and catecholamine assays. In TG mice, hypertrophy of the right ventricle was evident (+67%) but the LV was only mildly affected (+17%). LV fractional shortening and fractional area change from echocardiography were similar between the two groups. Catheterisation experiments revealed that LV ±dP/dt were comparable between TG and WT mice, and responded similarly upon isoproterenol stimulation indicating lack of 
-adrenergic receptor dysfunction. Whilst, norepinephrine levels in TG LV tissue were ~2-fold that of WT, TG plasma levels of DHPG, a neuronal norepinephrine metabolite, was 5-fold that of WT. A greater neuronal uptake activity was also observed in TG LV tissue. In conclusion, overexpression of NGF in the heart leads to sympathetic hyperinnervation that is not associated with detrimental effects on LV performance, likely due to concomitantly enhanced norepinephrine neuronal uptake.
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M. Esler and D. Kaye Sympathetic Nervous System Neuroplasticity Hypertension, February 1, 2006; 47(2): 143 - 144. [Full Text] [PDF]
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