Effects of Aging on the Responsiveness of the Human Cardiac Sympathetic Nerves to Stressors
Abstract
Background Aging increases human sympathetic nervous activity at rest. Because of the probable importance of neural stress responses in the heart as triggers for clinical end points of coronary artery disease, it is pertinent to investigate whether sympathetic nervous responses to stresses are increased by aging. Methods and Results We applied kinetic methods for measuring the fluxes to plasma of neurochemicals relevant to sympathetic neurotransmission in younger (aged 20 to 30 years) and older (aged 60 to 75 years) healthy men during mental stress (difficult mental arithmetic), isometric exercise (sustained handgrip), and dynamic exercise (supine cycling). The increase in total norepinephrine spillover to plasma with mental stress was unaffected by age. In contrast, the increase in cardiac norepinephrine spillover was two to three times higher in the older subjects (P<.05). The probable mechanism of this higher cardiac norepinephrine spillover was reduced neuronal reuptake of the transmitter, because age had no influence on the overflow of the norepinephrine precursor, dihydroxyphenylalanine, or intraneuronal metabolite, dihydroxyphenylglycol (levels of these two substances reflect rates of cardiac norepinephrine synthesis and intraneuronal metabolism), and the transcardiac extraction of plasma radiolabeled norepinephrine was lower in the older subjects (P<.05). An almost identical pattern of neurochemical response was seen with isometric exercise. During cycling, total norepinephrine spillover was 16% lower in the older men, but cardiac norepinephrine spillover was 53% higher. Conclusions Reduced norepinephrine reuptake increases the overflow of the neurotransmitter to plasma from the aging heart during stimulation of the cardiac sympathetic outflow. Failure of transmitter inactivation at postjunctional receptors with aging would amplify the neural signal, and in the presence of myocardial disease could trigger adverse stress-induced cardiovascular events, particularly when accompanied by an age-dependent reduction in vagal tone. Reduction of postsynaptic adrenergic responsiveness with aging, however, might protect against this, as indicated by our finding that in no case was the heart rate increase during stress greater in older men, despite their having larger increases in cardiac norepinephrine spillover.
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Aging increases sympathetic activity, evident in higher multiunit sympathetic nerve firing measured by microneurography and in higher cardiac norepinephrine spillover, both at rest and during mental stress.
“Aging does increase sympathetic activity, evident in higher multiunit sympathetic nerve firing measured by microneurography 77 and in higher cardiac norepinephrine spillover, both at rest and during mental stress.90”
From Obesity Paradox in Hypertension: Is This Because Sympathetic Activation in Obesity-Hypertension Takes a Benign Form? (2018) · cites this paper as [90]
Aging produces impairment of neuronal norepinephrine reuptake.
“In addition, aging produces impairment of neuronal norepinephrine reuptake.90”
From Obesity Paradox in Hypertension: Is This Because Sympathetic Activation in Obesity-Hypertension Takes a Benign Form? (2018) · cites this paper as [90]
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- Authors
- Esler, M. D., Thompson, J. M., Kaye, D. M., Turner, A. G., Jennings, G. L., Cox, H. S., Lambert, G. W., & Seals, D. R.
- Affiliations
- University of Colorado Boulder (US)
- ORCID
- Venue
- Circulation
- Published
- 1995-01-15
- Volume
- 91
- Issue
- 2
- Pages
- 351-358
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2011392057
- Cited by
- 183
- References
- 51
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 5 · 2023: 6 · 2022: 1 · 2021: 6 · 2020: 3 · 2019: 6 · 2018: 8 · 2017: 6 · 2016: 7 · 2015: 8 · 2014: 2 · 2013: 6 · 2012: 3
- FWCI
- 5.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01-AG-06537-07, R01AG006537)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- aging, cardiac sympathetic nervous system, norepinephrine spillover, norepinephrine uptake, psychological stress, isometric exercise, dynamic exercise, DOPA, DOPAC, vagal tone, coronary artery disease, heart rate response
- MeSH terms
- Adult, Aged, Aging, Blood Pressure, Dihydroxyphenylalanine, Heart, Heart Rate, Humans, Male, Methoxyhydroxyphenylglycol, Middle Aged, Myocardium, Norepinephrine, Rest, Stress, Psychological, Sympathetic Nervous System, Exercise, Neurotransmitter Agents
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