doi: 10.1161/CIRCRESAHA.107.155861
© 2007 American Heart Association, Inc.
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Forever Young?
Nerve Growth Factor, Sympathetic Fibers, and Right Ventricle Pressure Overload
From the Division of Cardiology (N.F., N.P.), Johns Hopkins Medical Institutions, Baltimore, Md; Department of Pharmacology (D.B.H.), College of Medicine, East Tennessee State University, Johnson City; Dipartimento di Medicina Cliniica e Sperimentale (N.P.), Universita’ di Perugia, Perugia, Italy.
Correspondence to Nazareno Paolocci, MD, PhD, 835 Ross Bldg, Division of Cardiology, Johns Hopkins School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205. E-mail naz@jhmi.edu
See related article, pages 1755–1764
Key Words: sympathetic fibers • congestive heart failure • nerve growth factor • rejuvenation and hypertrophy
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
In addition to abnormalities such as structural/metabolic remodeling and Ca2+ mishandling, the failing heart has to cope with the hyperactivation of sympathetic efferent fibers. The latter is part of the more general neuroendocrine disorder typical of this syndrome, and can be because of: 1) reflex changes originating from altered neural inputs (baroreceptors and chemoreceptors); 2) increased levels of circulating hormones such as angiotensin II (Ang II); 3) central factors that may sustain and amplify these responses; and 4) Ang II generated locally within the heart.1 Although some components of the neuronal loop constituting the sympathetic reflex arch are not fully elucidated yet (for example, it is still unclear what is the afferent component of this circuitry), there is no doubt that norepinephrine (NE) spillover is among the major consequences of sympathetic hyperactivation in CHF. Despite the fact that the NE content of the myocardium from human failing heart is 50% less than that found in normal tissue,2 in untreated CHF patients the enhanced sympathetic nerve outflow leads to NE plasma concentrations that are 50 times higher than in normal subjects.3 The NE spillover can be attributed to increased rates of sympathetic fiber discharge and impaired NE reuptake into the sympathetic efferents.
Although increases in sympathetic activity can be beneficial during the early stage of heart failure, providing inotropic support and peripheral vasoconstriction, such compensation becomes maladaptive in the long term, affecting Ca2+ handling to decrease contractility4,5 and interfering with L-type calcium channel function to promote arrhythmias6 and cardiac sudden death.7
Related Article:
Circ. Res. 2007 100: 1755-1764.