Sympathoneural and haemodynamic characteristics of young subjects with mild essential hypertension
Abstract
OBJECTIVES: Whether muscle sympathetic nerve activity (MSNA) is increased in young subjects with mild essential hypertension has not been firmly established, and the potential haemodynamic correlates of any such increase have not been specifically investigated. The objectives of this study were to quantitate MSNA from the peroneal nerve of young subjects with mild hypertension, to determine the haemodynamic and neurohumoral correlates of sympathetic vasoconstrictor nerve traffic in such subjects, and to document the stability of these observations. DESIGN: Twelve young untrained subjects with mild essential hypertension (mean age 31 years, average clinic blood pressure 151/95 mmHg) and 11 age- and weight-matched normotensive subjects were studied on two sessions, at least 1 month apart, at the same time of day and under identical laboratory conditions. METHODS: Blood pressure (non-invasive), microneurography (MSNA; peroneal nerve), cardiac output and calculated total peripheral resistance (echocardiography and continuous-wave Doppler) and calf blood flow and resistance (plethysmography) were recorded during supine rest and assessed for condition and study order effects by two-way analysis of variance. Reproducibility of MSNA was quantified by the standard deviation of the mean difference (SDD) between the values obtained on the two study days. RESULTS: Muscle sympathetic nerve burst frequency and incidence, calf vascular resistance and cardiac output and index were significantly higher in hypertensive subjects, whereas heart rate, total peripheral resistance, plasma noradrenaline and plasma atrial natriuretic factor concentrations were similar in the two groups. There was no study order effect, in either group, on mean values for MSNA or these haemodynamic variables, but the SDD (day 1-day 2 variation) in muscle sympathetic burst frequency was significantly greater in hypertensive subjects. CONCLUSIONS: Mild essential hypertension in young subjects can be characterized by augmented MSNA as measured from the peroneal nerve, greater between-session variation in sympathetic burst frequency (but no study order effect), and increased calf vascular resistance and cardiac output. These sympathoneural and haemodynamic alterations are potential mechanisms of primary hypertension.
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Subsequent studies employing microneurography or measurements of norepinephrine spillover in young adults with borderline or established hypertension have demonstrated marked sympathetic activation.
“Subsequent studies employing microneurography or measurements of norepinephrine spillover in young adults with borderline or established hypertension have also demonstrated marked sympathetic activation28,32,33.”
From The Sympathetic Nervous System Alterations in Human Hypertension (2015) · cites this paper as [33]
The sympathetic neural outflow is commonly activated also to the heart and skeletal muscle vasculature, but renal sympathetic activation is central to hypertension pathogenesis.
“The sympathetic neural outflow is commonly activated also to the heart, shown with selective cardiac norepinephrine spillover measurements28, and to the skeletal muscle vasculature, demonstrated with microneurographic nerve traffic recording32,33,38–46, but it is the renal sympathetic activation which is central to hypertension pathogenesis96–97.”
From The Sympathetic Nervous System Alterations in Human Hypertension (2015) · cites this paper as [33]
Patients with hypertension have a greater frequency of MSNA bursts than properly matched normotensive subjects.
“Despite the difficulty of establishing that every unit within a burst has a vasoconstrictor role, there is a wealth of evidence to suggest that patients with hypertension have a greater frequency of MSNA bursts than properly matched normotensive subjects (15,25–27).”
From Hypertensive left ventricular hypertrophy: relation to peripheral sympathetic drive (2001) · cites this paper as [27]
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Blood pressure regulation and micronutrients.
Dakshinamurti, K., & Dakshinamurti, S. (2001) · PubMed · doi:10.1079/nrr200116 · Cited by 21 · see citing works
Guild, S., Barrett, C. J., & Malpas, S. C. (2005) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.2005.04207.x · Cited by 20 · see citing works
The sympathetic nervous system in renovascular hypertension: lead actor or ‘bit’ player?
Grassi, G. M., & Esler, M. (2002) · Journal of Hypertension · doi:10.1097/00004872-200206000-00013 · Cited by 20 · see citing works
Hemodynamic circulatory patterns in young patients with predominantly diastolic hypertension
Romero, C. A., Alfie, J., Galarza, C., Waisman, G. D., Peixoto, A. J., Tabares, A. H., & Orías, M. (2013) · Journal of the American Society of Hypertension · doi:10.1016/j.jash.2013.01.001 · Cited by 18 · see citing works
Baroreflex activation therapy systems: current status and future prospects
Seravalle, G., Dell’Oro, R., & Grassi, G. M. (2019) · Expert Review of Medical Devices · doi:10.1080/17434440.2019.1697230 · Cited by 18 · see citing works
Weiss, M., Bouchoucha, S., Aiad, F., Ayme‐Dietrich, E., Dali‐Youcef, N., Bousquet, P., Greney, H., & Niederhoffer, N. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00021.2015 · Cited by 19 · see citing works
Sympathetic modulation as a goal of antihypertensive treatment: from drugs to devices
Grassi, G. M. (2023) · Journal of Hypertension · doi:10.1097/hjh.0000000000003538 · Cited by 17 · see citing works
“The consistent evidence collected can be summarized as follows First, different methodological approaches to investigate human sympathetic neural function have shown that a state of sympathetic overactivity characterizes the hypertensive evident [1–13].”
Central nervous system mechanisms of salt-sensitive hypertension
Feng, Y., Pan, S., Verma, H., Zheng, H., Plata, A. A., Zubcevic, J. A., & Leenen, F. H. H. (2025) · Physiological Reviews · doi:10.1152/physrev.00035.2024 · Cited by 20 · see citing works
Maciorowska, M., Krzesiński, P., Wierzbowski, R., Uziębło‐Życzkowska, B., & Gielerak, G. G. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11133767 · Cited by 16 · see citing works
“Floras and Hara [29] demonstrated increased ANS activity (assessed via microneurography) and increased cardiac output in younger patients with AH (mean age 31 years, mean BP 151/95 mmHg) in comparison with the normotensive ones.”
ResultThe central sympathetic nervous system in hypertension
Mancia, G., & Grassi, G. M. (2013) · Handbook of clinical neurology · doi:10.1016/b978-0-444-53491-0.00026-2 · Cited by 14 · see citing works
Renal sympathetic nerve activity in the development of hypertension
Malpas, S. C., Ramchandra, R., Guild, S., McBryde, F. D., & Barrett, C. J. (2006) · Current Hypertension Reports · doi:10.1007/s11906-006-0057-0 · Cited by 15 · see citing works
“Direct recordings of muscle sympathetic activity in humans also reveal increased activity in subjects with borderline hypertension and young normotensives with a family history of hypertension, but not in established hypertensives [12, 13 ].”
BackgroundUse of Microneurography to Evaluate Sympathetic Activity in Hypertension: A Brief Review
Yucha, C. B. (2000) · Applied Psychophysiology and Biofeedback · doi:10.1023/a:1009537506603 · Cited by 14 · see citing works
“In summary, resting MSNA activity is greater in hypertensives than normotensives (Anderson et al., 1989; Floras & Hara, 1993; Grassi, Cattaneo, Seravalle, Lanfranchi, & Mancia, 1998; Grassi, Colombo, et al., 1998; Yamada et al., 1989), greater in males than in females (Jones et al., 1996; Ng et al., 1993), and increas…”
BackgroundPagani, M. (2000) · Current Medical Research and Opinion · doi:10.1185/0300799009117032 · Cited by 14 · see citing works
Macrophages Can Drive Sympathetic Excitability in the Early Stages of Hypertension
Neely, O. C., Domingos, A. I., & Paterson, D. J. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.807904 · Cited by 12 · see citing works
Stevenson, E. R., Johns, E. M. C., Marques, F. Z., Jackson, K. L., Davern, P. J., Evans, R. G., & Head, G. A. (2016) · Journal of Hypertension · doi:10.1097/hjh.0000000000001210 · Cited by 12 · see citing works
Does QTc Interval Predict the Response to β-Blockers and Calcium Channel Blockers in Hypertensives?
Lamarre-Cliché, M., Lacourcière, Y., de Champlain, J., Poirier, L., & Larochelle, P. M. (2003) · Heart Disease · doi:10.1097/01.hdx.0000080716.21869.a1 · Cited by 9 · see citing works
From Brain to Blood Vessel: Insights From Muscle Sympathetic Nerve Recordings
Floras, J. S. (2021) · Hypertension · doi:10.1161/hypertensionaha.121.16490 · Cited by 9 · see citing works
Self-citationInsulin Resistance and Blood Pressure
Ferrannini, E. (1999) · Humana Press eBooks · doi:10.1007/978-1-59259-716-1_15 · Cited by 9 · see citing works
Differentiation in the Angiotensin II Receptor 1 blocker class on autonomic function
Krum, H. (2001) · Current Hypertension Reports · doi:10.1007/s11906-001-0067-x · Cited by 9 · see citing works
“More sophisticated measures of sympathetic activity, such as tritiated norepinephrine spillover rate [2] and direct recording of muscle sympathetic nerve activity via microneurography [3], have also been shown to be higher in hypertensive patients than in normotensive persons.”
Background
- Authors
- Floras, J. S., & Hara, K.
- Affiliations
- Toronto General Hospital (CA)
- ORCID
- Hara, Kazuhiro
- Venue
- Journal of Hypertension
- Published
- 1993-06
- Volume
- 11
- Issue
- 6
- Pages
- 647-655
- ISSN
- 0263-6352 (ISSN-L)
- OpenAlex
- W1965263133
- Cited by
- 137
- References
- 0
- Citations by year
- 2025: 2 · 2023: 4 · 2022: 3 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 6 · 2017: 5 · 2016: 5 · 2015: 9 · 2014: 6 · 2013: 9 · 2012: 4
- FWCI
- 2.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Hypertension (publishedVersion)
- PubMed (publishedVersion)
- 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
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Keywords
- essential hypertension, muscle sympathetic nerve activity, sympathetic nervous system, hemodynamics, peroneal nerve, cardiac output, norepinephrine, atrial natriuretic peptide, reproducibility, young adults
- MeSH terms
- Adult, Female, Hemodynamics, Humans, Hypertension, Male, Muscles, Sympathetic Nervous System
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