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The ‘adrenaline hypothesis’ of hypertension revisited: evidence for adrenaline release from the heart of patients with essential hypertension
Abstract
OBJECTIVE: Whether adrenaline acts as a sympathetic nervous cotransmitter in humans and stimulates beta2-adrenoceptors to augment neuronal noradrenaline release remains a subject of considerable dispute. The aim of this study was to test if adrenaline is released from regional sympathetic nerves (in the heart) in patients with essential hypertension, and to investigate whether locally released adrenaline might enhance cardiac noradrenaline release. METHODS: Using dual isotope dilution methodology, adrenaline and noradrenaline plasma kinetics was measured for the whole body and in the heart in 13 untreated patients with essential hypertension and 27 healthy volunteers. All research participants underwent cardiac catheterization under resting conditions. RESULTS: At rest, there was negligible adrenaline release from the sympathetic nerves of the heart in healthy subjects, 0.27 +/- 1.62 ng/min. In contrast, in patients with essential hypertension, adrenaline was released from the heart at a rate of 1.46 +/- 1.73 ng/min, equivalent on a molar basis to approximately 5% of the associated cardiac noradrenaline spillover value. Cardiac noradrenaline spillover was higher in hypertensive patients, 24.9 +/- 17.0 ng/min compared to 15.4 +/- 11.7 ng/min in healthy volunteers (P< 0.05). Among patients, rates of cardiac adrenaline and noradrenaline spillover correlated directly (r= 0.59, P< 0.05). CONCLUSIONS: This study, in demonstrating release of adrenaline from the heart in patients with essential hypertension, and in disclosing a proportionality between rates of cardiac adrenaline and noradrenaline release, provides perhaps the most direct evidence to date in support of the 'adrenaline hypothesis' of essential hypertension.
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“This outward epinephrine flux, measurable by isotope dilution analogous to the measurement of norepinephrine spillover, averaged 2 ng/min in normal-weight essential hypertension, 41 equivalent to 5% to 15% of the accompanying neuronal norepinephrine release.”
From Obesity Paradox in Hypertension: Is This Because Sympathetic Activation in Obesity-Hypertension Takes a Benign Form? (2018) · cites this paper as [41]
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Metadata
- Authors
- Rumantir, M. S., Jennings, G. L., Lambert, G. W., Kaye, D. M., Seals, D. R., & Esler, M. D.
- Affiliations
- The Alfred Hospital (AU)
- University of Colorado Boulder (US)
- Corresponding author
- Rumantir, Magdalena S.
- Venue
- Journal of Hypertension
- Published
- 2000-06
- Volume
- 18
- Issue
- 6
- Pages
- 717-723
- ISSN
- 0263-6352 (ISSN-L)
- OpenAlex
- W1965533587
- Cited by
- 72
- References
- 27
- Citations by year
- 2023: 1 · 2022: 1 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 3 · 2015: 4 · 2013: 2 · 2012: 3
- FWCI
- 4.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AGO6537, R01AG006537)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- 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
- essential hypertension, adrenaline secretion, cardiac sympathetic nerves, noradrenaline spillover, beta2-adrenergic receptor
- MeSH terms
- Adult, Epinephrine, Female, Heart Conduction System, Humans, Hypertension, Male, Middle Aged, Models, Cardiovascular, Myocardium, Norepinephrine, Reference Values, Sympathetic Nervous System
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