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Cited by 211Blood Pressure and Hypertension StudiesDiabetes, Cardiovascular Risks, and LipoproteinsCardiovascular and exercise physiology

Sympathetic Neural Activation in Nondiabetic Metabolic Syndrome and Its Further Augmentation by Hypertension

Huggett, Robert J., Burns, Joanna, Mackintosh, Alan F., Mary, David A.S.G.·2004·Hypertension
DOI 10.1161/01.hyp.0000147893.08533.d8
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Abstract

Hypertension is a major cardiovascular risk factor in the metabolic syndrome (MS) in which the presence of insulin resistance, glucose intolerance, abnormal lipoprotein metabolism, and central obesity all confer an increased risk. Because essential hypertension (EHT), insulinemia, and visceral fat are associated with sympathetic hyperactivity, which is itself known to increase cardiovascular risk, the aim of this study was to see if MS is a state of sympathetic nerve hyperactivity and if the additional presence of EHT intensifies this hyperactivity. In 69 closely matched subjects, comprising hypertensive MS (MS+EHT, 18), normotensive MS (MS-EHT, 17), hypertensives without MS (EHT, 16), and normotensive controls without MS (NC, 18), we measured resting muscle sympathetic nerve activity (MSNA) as assessed from multiunit discharges and from single units with defined vasoconstrictor properties (s-MSNA). The s-MSNA in MS+EHT (76±3.1 impulses/100 beats) was greater (at least P <0.01) than in MS-EHT (62±3.2 impulses/100 beats) and in EHT (60±2.3 impulses/100 beats), and all these were significantly greater (at least P <0.01) than in NC (46±2.7 impulse/100 beats). The multi-unit MSNA followed a similar trend. These findings suggest that MS is a state of sympathetic nerve hyperactivity and that the additional presence of hypertension further intensifies this hyperactivity. The degree of sympathetic hyperactivity seen in this study could be argued at least partly to contribute to the higher cardiovascular risk and metabolic abnormalities seen in MS+EHT patients.

AI snapshot

Written from the paper’s full text.

TL;DR

In nondiabetic metabolic syndrome, resting sympathetic nerve activity is increased, and the additional presence of hypertension further augments it. The authors conclude this sympathetic hyperactivity may contribute to higher cardiovascular risk and metabolic abnormalities in MS+EHT.

Key findings

  • Resting single-unit muscle sympathetic nerve activity (s-MSNA) was 76±3.1 impulses/100 beats in MS+EHT, greater than 62±3.2 in MS-EHT and 60±2.3 in EHT (at least P<0.01), and all three groups exceeded NC at 46±2.7 impulses/100 beats (at least P<0.01); multiunit MSNA followed a similar trend.
  • MS+EHT had the highest sympathetic activity, significantly greater than MS-EHT, which was similar to EHT; s-MSNA hyperactivity was increased by ≈65% in MS+EHT and ≈35% in MS-EHT versus NC.
  • MS groups had greater fasting glucose, insulin, HOMA-IR, triglycerides, and lower HDL cholesterol than EHT and NC; the only difference between MS+EHT and MS-EHT was slightly greater triglycerides in MS+EHT.
  • Plasma insulin and HOMA-IR positively correlated with s-MSNA and MSNA in MS+EHT (r 0.41–0.45; at least P<0.04) and MS-EHT (r 0.49–0.53; at least P<0.02); no significant correlations were found with waist circumference, waist/hip ratio, fasting glucose, triglycerides, or HDL (r −0.34 to 0.42; at least P>0.05).

Methods

  • Cross-sectional comparison of 69 white subjects with complete data (from 72 examined; 3 excluded because stable single-unit microneurographic data could not be obtained): MS+EHT n=18, MS-EHT n=17, EHT n=16, NC n=18. MS was defined by NCEP ATP III criteria; diabetes was excluded.
  • Resting postganglionic muscle sympathetic nerve activity was recorded from the right peroneal nerve by microneurography, quantified as multiunit MSNA and single-unit s-MSNA with vasoconstrictor properties; simultaneous ECG, Finometer arterial pressure, strain-gauge calf blood flow, and calf vascular resistance were measured, and baroreceptor reflex sensitivity was obtained from Valsalva.
  • One-way ANOVA with Newman-Keuls post-tests compared groups; least-square technique assessed linear relationships; P<0.05 was significant; data are mean±SEM.

Limitations

  • Stated: antihypertensive therapy differed between groups and was not withdrawn; the authors state they cannot entirely exclude an influence of ACE inhibitors, ARBs, thiazide diuretics, or beta-blockers, although they argue these agents could not entirely cause the excessive sympathetic hyperactivity.
  • Stated: findings may not extrapolate beyond white subjects because insulinemia and sympathetic nerve activity can differ by ethnicity; the authors also state there may be differences in sympathetic output to regions other than the leg.
  • Stated/evident: the study is cross-sectional and the authors state their findings do not establish a causal relationship between MS and sympathetic activity; no longitudinal or interventional causal test was performed.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1161/01.hyp.0000147893.08533.d8

Cites

44 of 44 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 56 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    s-MSNA was greater in MS+EHT (76±3.1 impulses/100 beats) than in NC (46±2.7 impulses/100 beats), at least P<0.01.

    “The s-MSNA in MSϩEHT (76Ϯ3.1 impulses/100 beats) was greater (at least PϽ0.01) than in MS-EHT (62Ϯ3.2impulses/100 beats) and in EHT (60Ϯ2.3impulses/100 beats), and all these were significantly greater (at least PϽ0.01) than in NC (46Ϯ2.7 impulse/100 beats).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: s-MSNA reflects the mean resting sympathetic nerve frequency supplying the peripheral vessels.
  • Findingown data

    s-MSNA was greater in MS+EHT (76±3.1 impulses/100 beats) than in EHT (60±2.3 impulses/100 beats), at least P<0.01.

    “The s-MSNA in MSϩEHT (76Ϯ3.1 impulses/100 beats) was greater (at least PϽ0.01) than in MS-EHT (62Ϯ3.2impulses/100 beats) and in EHT (60Ϯ2.3impulses/100 beats), and all these were significantly greater (at least PϽ0.01) than in NC (46Ϯ2.7 impulse/100 beats).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: s-MSNA reflects the mean resting sympathetic nerve frequency supplying the peripheral vessels.
  • Findingown data

    s-MSNA was greater in MS+EHT (76±3.1 impulses/100 beats) than in MS-EHT (62±3.2 impulses/100 beats), at least P<0.01.

    “The s-MSNA in MSϩEHT (76Ϯ3.1 impulses/100 beats) was greater (at least PϽ0.01) than in MS-EHT (62Ϯ3.2impulses/100 beats) and in EHT (60Ϯ2.3impulses/100 beats), and all these were significantly greater (at least PϽ0.01) than in NC (46Ϯ2.7 impulse/100 beats).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: s-MSNA reflects the mean resting sympathetic nerve frequency supplying the peripheral vessels.
  • Findingown data

    Multi-unit MSNA followed a similar trend across groups.

    “The multi-unit MSNA followed a similar trend.”
    Quote in the paperNot a substantial claim
  • Findingown data

    s-MSNA was greater in MS-EHT (62±3.2 impulses/100 beats) than in NC (46±2.7 impulses/100 beats), at least P<0.01.

    “The s-MSNA in MSϩEHT (76Ϯ3.1 impulses/100 beats) was greater (at least PϽ0.01) than in MS-EHT (62Ϯ3.2impulses/100 beats) and in EHT (60Ϯ2.3impulses/100 beats), and all these were significantly greater (at least PϽ0.01) than in NC (46Ϯ2.7 impulse/100 beats).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: s-MSNA reflects the mean resting sympathetic nerve frequency supplying the peripheral vessels.
  • May combine two claims. 18
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim. 15

  • May combine two claims. The quote only partly states this claim.

    Findingcitation

    Baroreceptor reflex sensitivity was lower in the hypertensive groups (EHT and MS+EHT) than in the normotensive groups (NC and MS-EHT); specifically, MS+EHT was similar to EHT, and both were less than MS-EHT and NC.

    “The EHT groups had lower baroreceptor reflex sensitivity than the other 2 groups as previously reported.4,7”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [4]

      Not checked in the free run.

    • cites [7] source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    CVR levels differed in concert with sympathetic hyperactivity, being highest in MS+EHT and greater in MS-EHT and EHT than NC.

    “Despite the vasodilating agents taken by the hypertensive groups, the level of CVR showed differences that were in concert with the sympathetic hyperactivity observed, being highest in MSϩEHT and greater in MS-EHT and EHT than NC (Table 2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The mean frequency of s-MSNA and MSNA per minute and per 100 cardiac beats was significantly greater in MS-EHT and MS+EHT than in NC.

    “The mean frequency of s-MSNA and MSNA per minute and per 100 cardiac beats was significantly greater in MS-EHT and MSϩEHT than in NC (Table, 2; Figure 2).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The MS groups (MS+EHT and MS-EHT) had greater fasting glucose, insulin, HOMA-IR, triglycerides, and lower HDL cholesterol than the EHT and NC groups.

    “The MS groups (MSϩEHT and MS-EHT) had greater fasting glucose, insulin, HOMA-IR, triglycerides, and lower HDL cholesterol than the EHT and NC groups (Table 1).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The s-MSNA hyperactivity of MS+EHT and MS-EHT was increased by approximately 65% and 35%, respectively, compared with NC.

    “The s-MSNA hyperactivity of MSϩEHT and MS-EHT was increased by Ϸ65% and 35%, respectively, when compared with that in NC.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The MS+EHT group had the highest sympathetic activity level, significantly greater than MS-EHT, which in turn was similar to EHT.

    “The MSϩEHT group had the highest sympathetic activity level, and this was significantly greater than that in MS-EHT, which in turn was similar to that in EHT.”
    • Also stated in: § Discussion · plain
      “Second, activation of vasoconstrictor sympathetic activity in MSϩEHT was greater than that seen in either EHT or MS-EHT alone.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Sympathetic neural activation is increased in nondiabetic metabolic syndrome and is further augmented by hypertension.

    “the finding of increased peripheral sympathetic nerve activity in MS and its further augmentation by the presence of EHT”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Insulin resistance was assessed by the previously validated homeostasis model assessment (HOMA).

    “Insulin resistance was assessed by the previously validated 16,17 homeostasis model assessment (HOMA)”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [16] source

      Not checked in the free run.

    • cites [17] source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    MSNA bursts contain different efferent units, including those recruited through the operation of reflex mechanisms.

    “However, the MSNA bursts contain different efferent units, including those recruited through the operation of reflex mechanisms, 4 and their data make our findings comparable with other publications in terms of potential confounding factors.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [4]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    This was confirmed by simultaneous measurement of calf blood flow and calf vascular resistance.

    “This was confirmed by simultaneous measurement of CBF and CVR.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    In all subjects, measured variables were obtained in an identical manner as previously published.

    “In all subjects, the measured variables were obtained in an identical manner as has been published previously.4,7”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [4]

      Not checked in the free run.

    • cites [7] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The intraobserver reproducibility of calf blood flow measurement in this laboratory was 2.4% of the measurement value.

    “The intraobserver reproducibility of CBF measurement in this laboratory, obtained as twice 95% confidence interval of differences between repeated within-session plethysmography, amounted to 2.4% of the value of the measurement.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Sympathetic activation is associated with individual components of metabolic syndrome, including visceral obesity, insulinemia, essential hypertension, and type 2 diabetes.

    “Sympathetic activation has already been associated with many of the individual components of the MS, such as visceral obesity, 5 insulinemia, 6 EHT, [1][2][3][4] and type 2 diabetes.7”
    • Also stated in: § Abstract · plain
      “Because essential hypertension (EHT), insulinemia, and visceral fat are associated with sympathetic hyperactivity”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [5] source

      Not checked in the free run.

    • cites [6] source

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    • cites [1][2][3][4]

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  • Classified as probably not a substantial claim.

    Premisecitation

    Sympathetic activation in essential hypertension contributes to cardiovascular risk.

    “sympathetic activation in EHT is believed to contribute to cardiovascular risk.13,14”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [13] source

      Not checked in the free run.

    • cites [14]

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Only vasoconstrictor discharge was accepted after showing appropriate responses to spontaneous arterial pressure changes, the Valsalva maneuver, isometric handgrip exercise, and cold pressor tests.

    “Only vasoconstrictor discharge was accepted after showing appropriate responses to spontaneous arterial pressure changes, the Valsalva maneuver, isometric handgrip exercise, and cold pressor tests.4,7,19,20”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [4]

      Not checked in the free run.

    • cites [7] source

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    • cites [19] source

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    • cites [20] source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Complete microneurographic data were obtained from 69 of 72 subjects; 3 subjects were excluded because stable single-unit activity could not be obtained.

    “Stable microneurographic data to obtain single unit activity could not be obtained in 3 subjects, and complete data were therefore obtained from 69 subjects.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    There may be differences in the sympathetic output to regions other than the leg in these patients.

    “There may be differences in the sympathetic output to regions other than the leg in our patients.2,3”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [2]

      Not checked in the free run.

    • cites [3] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    The results are consistent with other reported findings in conditions related to MS despite involving different populations, regions, and techniques.

    “However, it is noteworthy to mention that our results are consistent with other reported findings in conditions related to MS despite involving different populations, regions, and techniques.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductcitation

    The four groups had similar heart rate levels, minimizing its effect on sympathetic nerve activity.

    “Furthermore, the 4 groups had similar heart rate levels, thus minimizing its effect on sympathetic nerve activity.26”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [26] source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    Similar results were obtained when the data were analyzed according to gender or while separately excluding patients taking ACE inhibitors, ARBs, thiazide diuretics, and β-blockers.

    “Similar results were obtained when the data were analyzed according to gender or while separately excluding patients taking ACE inhibitors, ARBs, thiazide diuretics, and ␤-blockers.”
    • Also stated in: § Discussion · plain
      “Analyzing the data in patients not taking ARB or ␤-blocking agents did not affect our findings.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    MS is a state of sympathetic nerve hyperactivity, particularly in the presence of hypertension.

    “These considerations are consistent with our findings of MS being a state of sympathetic nerve hyperactivity, particularly in the presence of hypertension.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The metabolic abnormalities found in MS are associated with an enhanced sympathetic drive that is further intensified by the presence of hypertension.

    “These findings suggest that the metabolic abnormalities found in MS are associated with an enhanced sympathetic drive that is further intensified by the presence of hypertension.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Obesity in combination with EHT has been found to either increase MSNA or have no effect.

    “Also, obesity in combination with EHT has been found to either increase MSNA 29 or have no effect.30”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [29]

      Not checked in the free run.

    • cites [30]

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  • May combine two claims.

    Interpretationreasoning

    Although an effect of medications in the two hypertensive groups cannot be completely excluded, they could not have entirely caused the excessive sympathetic hyperactivity.

    “Therefore, although we cannot completely exclude an effect of medications in our 2 hypertensive groups, they could not have entirely caused the excessive sympathetic hyperactivity.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [22] source

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    • cites [23] source

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    • cites [24] source

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    • cites [25] source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    ARBs may decrease MSNA in hypertensive patients.

    “Although we cannot entirely exclude some influence of these agents, it is known in hypertensive patients that chronic ACE inhibitor therapy does not affect MSNA levels, 22 ARBs may decrease it, 23 and ␤-blockers may have no effect or decrease MSNA.24,25”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [23] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    The study did not test the risk of, or differences in, regional sympathetic activation in the patients.

    “Although we did not test the risk of, or differences in, regional sympathetic activation in our patients”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Patients with metabolic syndrome or essential hypertension have a high cardiovascular risk.

    “It is already known that MS or EHT patients have a high cardiovascular risk”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [11] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    β-blockers may have no effect or decrease MSNA in hypertensive patients.

    “Although we cannot entirely exclude some influence of these agents, it is known in hypertensive patients that chronic ACE inhibitor therapy does not affect MSNA levels, 22 ARBs may decrease it, 23 and ␤-blockers may have no effect or decrease MSNA.24,25”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [24] source

      Not checked in the free run.

    • cites [25] source

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28 of 28

  • The paper relies on this without support.

    s-MSNA reflects the mean resting sympathetic nerve frequency supplying the peripheral vessels.

    “We measured both s-MSNA and MSNA frequencies because s-MSNA reflects the mean resting sympathetic nerve frequency supplying the peripheral vessels.”
1 of 1

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The presence of hypertension in addition to other components of the metabolic syndrome was associated with further increases in single fiber firing and multifiber muscle sympathetic nerve activity.

    “The presence of hypertension in addition to other components of the metabolic syndrome was associated with further increases in single fiber firing and multifiber muscle sympathetic nerve activity.”

    From The Sympathetic Nervous System Alterations in Human Hypertension (2015) · cites this paper as [73]

  • Patients with metabolic syndrome without hypertension had increased muscle sympathetic nerve activity (specifically increased single fiber firing) when compared to a control group matched for body weight and lacking the metabolic syndrome.

    “Huggett et al73 demonstrated that patients with metabolic syndrome without hypertension had increased muscle sympathetic nerve activity (specifically increased single fiber firing) when compared to a control group matched for body weight and lacking the metabolic syndrome.”

    From The Sympathetic Nervous System Alterations in Human Hypertension (2015) · cites this paper as [73]

Cites

Flagged first, then by citations

Research works printed but not linked: 5

  1. 10.1161/circ.100.12.1305 · DOI
  2. 10.1161/hyp.34.4.724 · DOI
  3. 10.1161/hyp.36.4.538 · DOI
  4. 10.1161/hyp.27.2.276 · DOI
  5. 10.1161/hyp.36.4.531 · DOI

Cited by

Sorted by citations

Related

Authors
Huggett, R. J., Burns, J., Mackintosh, A. F., & Mary, D. A. S. G.
Affiliations
St James's University Hospital (GB)
ORCID
Mackintosh, Alan F.
Venue
Hypertension
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2004-12
Volume
44
Issue
6
Pages
847-852
ISSN
  • 0194-911X (ISSN-L)
  • 1524-4563
DOI
10.1161/01.hyp.0000147893.08533.d8
OpenAlex
W2166344703
Cited by
211
References
44
Citations by year
2026: 2 · 2025: 2 · 2024: 2 · 2023: 7 · 2022: 5 · 2021: 8 · 2020: 3 · 2019: 5 · 2018: 5 · 2017: 10 · 2016: 15 · 2015: 15 · 2014: 15 · 2013: 10 · 2012: 17
FWCI
8.92
Type
journal article
Language
en
Open access
closed
Locations
  • Hypertension (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
Keywords
metabolic syndrome, essential hypertension, muscle sympathetic nerve activity, cardiovascular risk, visceral fat, insulin resistance, non-diabetic patients
MeSH terms
Anthropometry, Blood Pressure, Electrodiagnosis, Female, Humans, Hypertension, Male, Middle Aged, Sympathetic Nervous System, Metabolic Syndrome

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