title: Preserved left ventricular structure and function in mice with cardiac sympathetic hyperinnervation.
abstract: Cardiac-specific overexpression of nerve growth factor (NGF), a neurotrophin, leads to sympathetic hyperinnervation of heart. As a consequence, adverse functional changes that occur after chronically enhanced sympathoadrenergic stimulation of 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- to 6-mo-old transgenic (TG) mice that overexpress NGF in 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 left ventricle was only mildly affected (+17%). Left ventricular (LV) fractional shortening and fractional area change values as indicated by echocardiography were similar between the two groups. Catheterization experiments revealed that LV +/-dP/dt values were comparable between TG and WT mice and responded similarly upon isoproterenol stimulation, which indicates lack of beta-adrenergic receptor dysfunction. Although norepinephrine levels in TG LV tissue were approximately twofold those of WT tissue, TG plasma levels of the neuronal norepinephrine metabolite dihydroxyphenylglycol were fivefold those of WT plasma. A greater neuronal uptake activity was also observed in TG LV tissue. In conclusion, overexpression of NGF in heart leads to sympathetic hyperinnervation that is not associated with detrimental effects on LV performance and is likely due to concomitantly enhanced norepinephrine neuronal uptake.
authors.affiliation: Experimental Cardiology Laboratory, Baker Heart Research Institute, P.O. Box 6492 St. Kilda Road Central, Melbourne, Victoria 8008, Australia.
authors.forename: Helen
authors.initials: H
authors.lastname: Kiriazis
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Du
authors.forename: Xinheng
authors.initials: X
authors.lastname: Feng
authors.forename: Elodie
authors.initials: E
authors.lastname: Hotchkin
authors.forename: Tanneale
authors.initials: T
authors.lastname: Marshall
authors.forename: Samara
authors.initials: S
authors.lastname: Finch
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Gao
authors.forename: Gavin
authors.initials: G
authors.lastname: Lambert
authors.forename: Julia K
authors.initials: JK
authors.lastname: Choate
authors.forename: David M
authors.initials: DM
authors.lastname: Kaye
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D004452:Echocardiography; D005260:Female; D015870:Gene Expression; D006321:Heart / Q000294:innervation* / Q000502:physiology; D017380:Hypertrophy, Right Ventricular / Q000000981:diagnostic imaging / Q000235:genetics / Q000503:physiopathology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000473:pathology; D020932:Nerve Growth Factor / Q000235:genetics*; D009638:Norepinephrine / Q000097:blood / Q000493:pharmacokinetics; D013564:Sympathetic Nervous System / Q000473:pathology* / Q000502:physiology; D014316:Tritium; D016277:Ventricular Function, Left
chemical_list: D000318:Adrenergic beta-Agonists; D014316:Tritium; D020932:Nerve Growth Factor; D007545:Isoproterenol; D009638:Norepinephrine