Cardiac Sympathetic Nerve Function in Congestive Heart Failure
Abstract
Background Increased availability of norepinephrine (NE) for activation of cardiac adrenoceptors (increased cardiac adrenergic drive) and depletion of myocardial NE stores may contribute to the pathophysiology and progression of congestive heart failure. This study used a comprehensive neurochemical approach to examine the mechanisms responsible for these abnormalities. Methods and Results Subjects with and without congestive heart failure received intravenous infusions of [ 3 H]NE. Cardiac spillover, reuptake, vesicular-axoplasmic exchange, and tissue stores of NE were assessed from arterial and coronary venous plasma concentrations of endogenous and [ 3 H]-labeled NE and dihydroxyphenylglycol. Tyrosine hydroxylase activity was assessed from plasma dopa, and NE turnover was assessed from measurements of NE metabolites. NE release and reuptake were both increased in the failing heart; however, the efficiency of NE reuptake was reduced such that cardiac spillover of NE was increased disproportionately more than neuronal release of NE. Cardiac NE stores were 47% lower and the rate of vesicular leakage of NE was 42% lower in the failing than in the normal heart. Cardiac spillover of dopa and NE turnover were increased similarly in congestive heart failure. Conclusions Increased neuronal release of NE and decreased efficiency of NE reuptake both contribute to increased cardiac adrenergic drive in congestive heart failure. Decreased vesicular leakage of NE, secondary to decreased myocardial stores of NE, limits the increase in cardiac NE turnover in CHF. Decreased NE store size in the failing heart appears to result not from insufficient tyrosine hydroxylation but from chronically increased NE turnover and reduced efficiency of NE reuptake and storage.
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Approximately 95% of norepinephrine released by the sympathetic nerves of the heart is recaptured by neuronal reuptake.
“Approximately 95% of norepinephrine released by the sympathetic nerves of the heart is recaptured by neuronal reuptake.”
From Obesity Paradox in Hypertension: Is This Because Sympathetic Activation in Obesity-Hypertension Takes a Benign Form? (2018) · cites this paper as [45]
Disposition of norepinephrine after its release is more dependent on neuronal reuptake in the heart than in all other organs.
“Disposition of norepinephrine after its release is more dependent on neuronal reuptake in the heart than in all other organs.45”
From Obesity Paradox in Hypertension: Is This Because Sympathetic Activation in Obesity-Hypertension Takes a Benign Form? (2018) · cites this paper as [45]
For cardiac sympathetic activation, the ranking is cardiac failure > normal-weight essential hypertension > depressive illness > aging.
“The ranking is as follows: for cardiac sympathetic activation, cardiac failure>normal-weight essential hypertension>depressive ill ness>aging.19,22,24,42,44,45,49,78”
From Obesity Paradox in Hypertension: Is This Because Sympathetic Activation in Obesity-Hypertension Takes a Benign Form? (2018) · cites this paper as [45]
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- Authors
- Eisenhofer, G., Friberg, P., Rundqvist, B., Quyyumi, A. A., Lambert, G., Kaye, D. M., Kopin, I. J., Goldstein, D. S., & Esler, M. D.
- Affiliations
- National Institutes of Health (US)
- ORCID
- Venue
- Circulation
- Published
- 1996-05
- Volume
- 93
- Issue
- 9
- Pages
- 1667-1676
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W1993675056
- Cited by
- 453
- References
- 39
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 5 · 2023: 6 · 2022: 8 · 2021: 13 · 2020: 14 · 2019: 12 · 2018: 9 · 2017: 9 · 2016: 16 · 2015: 13 · 2014: 18 · 2013: 25 · 2012: 15
- FWCI
- 13.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- congestive heart failure, cardiac sympathetic function, norepinephrine, norepinephrine uptake, norepinephrine spillover, norepinephrine turnover, tyrosine hydroxylase, DOPA, sympathetic nervous system
- MeSH terms
- Adolescent, Adult, Aged, Catecholamines, Dihydroxyphenylalanine, Exercise Test, Female, Heart, Heart Failure, Humans, Male, Methoxyhydroxyphenylglycol, Middle Aged, Myocardium, Norepinephrine, Receptors, Adrenergic, Sympathetic Nervous System, Tyrosine 3-Monooxygenase
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