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(Hypertension. 2006;47:209.)
© 2006 American Heart Association, Inc.

Original Articles

Injection of Nerve Growth Factor Into Stellate Ganglia Improves Norepinephrine Reuptake Into Failing Hearts

Michael M. Kreusser; Markus Haass; Sebastian J. Buss; Stefan E. Hardt; Stefan H. Gerber; Ralf Kinscherf; Hugo A. Katus; Johannes Backs

From the Departments of Cardiology (M.M.K., S.J.B., S.E.H., S.H.G., H.A.K., J.B.) and Anatomy (R.K.), University of Heidelberg, and Theresienkrankenhaus (M.H.), Mannheim, Germany.

Correspondence to Johannes Backs, Department of Cardiology, University of Heidelberg, INF 410, D-69120 Heidelberg, Germany. E-mail johannes.backs{at}web.de

An impairment of cardiac norepinephrine reuptake through the neuronal norepinephrine transporter promotes depletion of cardiac norepinephrine stores and local cardiac sympathetic activation in heart failure. Nerve growth factor regulates differentiation and survival of adult sympathetic cells and is decreased in failing hearts. We hypothesized that injection of nerve growth factor into stellate ganglia normalizes cardiac norepinephrine homeostasis in experimental heart failure. Rats with transverse aortic constriction characterized by heart failure, depleted cardiac norepinephrine stores, and impaired cardiac norepinephrine reuptake were used as an experimental model. Nerve growth factor (20 µg) or saline was directly injected into left stellate ganglia 4 weeks after transverse aortic constriction. Thirty-two hours after injection, determinants of cardiac norepinephrine homeostasis were measured. As compared with saline, nerve growth factor refilled depleted cardiac norepinephrine stores and improved cardiac [³H]-norepinephrine uptake into isolated perfused hearts of transverse aortic constricted rats. In addition, pharmacological blockade of the norepinephrine transporter led to a higher increase in the overflow of endogenous norepinephrine from hearts of nerve growth factor-injected than saline-injected transverse aortic constricted rats. Norepinephrine transporter mRNA levels and the density of cardiac sympathetic nerves were not changed. Thirty-two hours after nerve growth factor injection, echocardiography revealed an increase in fractional shortening as compared with 2 days before injection. In conclusion, nerve growth factor attenuates local cardiac sympathetic overdrive of hypertrophic hearts by improving cardiac norepinephrine reuptake and might represent a novel therapeutic principle in the treatment of heart failure.

Key Words: heart failure • neuroregulators • norepinephrine • sympathetic nervous system

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