Reflex sympathetic activation during static exercise is severely impaired in patients with myophosphorylase deficiency

Paul J. Fadel, Zhongyun Wang, Meryem Tuncel, Hitoshi Watanabe, Aamer Abbas, Debbie Arbique, Wanpen Vongpatanasin, Robert W. Haley, Ronald G. Victor, Gail Thomas

Research output: Contribution to journalReview article

25 Citations (Scopus)

Abstract

During static exercise, metabolites accumulate in the muscle interstitium where they stimulate chemosensitive afferent nerves that reflexly increase efferent muscle sympathetic nerve activity (MSNA) and blood pressure. In experimental animals, lactic acid potently stimulates the muscle metaboreflex, but its role in humans is more controversial. To determine if lactic acid is a critical mediator of metaboreflex activation in humans, we performed microelectrode recordings of MSNA in eight patients with myophosphorylase deficiency (McArdle's disease) who cannot metabolize intramuscular glycogen and do not generate lactic acid in exercising muscles. Each patient was matched with three healthy control subjects to maximize statistical power. In controls, 2 min of static handgrip performed at 33 % or 45 % of maximal voluntary contraction (MVC) produced intensity-dependent increases in MSNA (171 ± 22 % and 379 ± 95 %, respectively). In the patients, MSNA responses to static handgrip were markedly attenuated (33 ± 14 % at 33 % MVC; 32 ± 19 % at 45 % MVC; P < 0.05 vs. controls . Likewise, when static handgrip (30 % MVC) was performed to fatigue, MSNA increased by 366 ± 73 % in controls but only by 51 ± 14 % in patients (P < 0.05). Pressor responses to static handgrip were also attenuated in patients compared to controls, whereas heart rate responses were identical. In contrast to exercise, the MSNA responses to other reflex stimuli (the cold pressor test or Valsalva's manoeuvre) were similar in patients and controls. Together these data indicate that appropriate activation of glycogenolytic pathways is obligatory for normal metaboreflex-mediated sympathoexcitation during static exercise in humans.

Original languageEnglish (US)
Pages (from-to)983-993
Number of pages11
JournalJournal of Physiology
Volume548
Issue number3
DOIs
StatePublished - May 1 2003

Fingerprint

Glycogen Storage Disease Type V
Reflex
Exercise
Muscles
Lactic Acid
Deficiency Diseases
Valsalva Maneuver
Muscle Fatigue
Microelectrodes
Glycogen
Healthy Volunteers
Heart Rate
Blood Pressure

All Science Journal Classification (ASJC) codes

  • Physiology

Cite this

Fadel, Paul J. ; Wang, Zhongyun ; Tuncel, Meryem ; Watanabe, Hitoshi ; Abbas, Aamer ; Arbique, Debbie ; Vongpatanasin, Wanpen ; Haley, Robert W. ; Victor, Ronald G. ; Thomas, Gail. / Reflex sympathetic activation during static exercise is severely impaired in patients with myophosphorylase deficiency. In: Journal of Physiology. 2003 ; Vol. 548, No. 3. pp. 983-993.
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title = "Reflex sympathetic activation during static exercise is severely impaired in patients with myophosphorylase deficiency",
abstract = "During static exercise, metabolites accumulate in the muscle interstitium where they stimulate chemosensitive afferent nerves that reflexly increase efferent muscle sympathetic nerve activity (MSNA) and blood pressure. In experimental animals, lactic acid potently stimulates the muscle metaboreflex, but its role in humans is more controversial. To determine if lactic acid is a critical mediator of metaboreflex activation in humans, we performed microelectrode recordings of MSNA in eight patients with myophosphorylase deficiency (McArdle's disease) who cannot metabolize intramuscular glycogen and do not generate lactic acid in exercising muscles. Each patient was matched with three healthy control subjects to maximize statistical power. In controls, 2 min of static handgrip performed at 33 {\%} or 45 {\%} of maximal voluntary contraction (MVC) produced intensity-dependent increases in MSNA (171 ± 22 {\%} and 379 ± 95 {\%}, respectively). In the patients, MSNA responses to static handgrip were markedly attenuated (33 ± 14 {\%} at 33 {\%} MVC; 32 ± 19 {\%} at 45 {\%} MVC; P < 0.05 vs. controls . Likewise, when static handgrip (30 {\%} MVC) was performed to fatigue, MSNA increased by 366 ± 73 {\%} in controls but only by 51 ± 14 {\%} in patients (P < 0.05). Pressor responses to static handgrip were also attenuated in patients compared to controls, whereas heart rate responses were identical. In contrast to exercise, the MSNA responses to other reflex stimuli (the cold pressor test or Valsalva's manoeuvre) were similar in patients and controls. Together these data indicate that appropriate activation of glycogenolytic pathways is obligatory for normal metaboreflex-mediated sympathoexcitation during static exercise in humans.",
author = "Fadel, {Paul J.} and Zhongyun Wang and Meryem Tuncel and Hitoshi Watanabe and Aamer Abbas and Debbie Arbique and Wanpen Vongpatanasin and Haley, {Robert W.} and Victor, {Ronald G.} and Gail Thomas",
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Fadel, PJ, Wang, Z, Tuncel, M, Watanabe, H, Abbas, A, Arbique, D, Vongpatanasin, W, Haley, RW, Victor, RG & Thomas, G 2003, 'Reflex sympathetic activation during static exercise is severely impaired in patients with myophosphorylase deficiency', Journal of Physiology, vol. 548, no. 3, pp. 983-993. https://doi.org/10.1113/jphysiol.2003.039347

Reflex sympathetic activation during static exercise is severely impaired in patients with myophosphorylase deficiency. / Fadel, Paul J.; Wang, Zhongyun; Tuncel, Meryem; Watanabe, Hitoshi; Abbas, Aamer; Arbique, Debbie; Vongpatanasin, Wanpen; Haley, Robert W.; Victor, Ronald G.; Thomas, Gail.

In: Journal of Physiology, Vol. 548, No. 3, 01.05.2003, p. 983-993.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Reflex sympathetic activation during static exercise is severely impaired in patients with myophosphorylase deficiency

AU - Fadel, Paul J.

AU - Wang, Zhongyun

AU - Tuncel, Meryem

AU - Watanabe, Hitoshi

AU - Abbas, Aamer

AU - Arbique, Debbie

AU - Vongpatanasin, Wanpen

AU - Haley, Robert W.

AU - Victor, Ronald G.

AU - Thomas, Gail

PY - 2003/5/1

Y1 - 2003/5/1

N2 - During static exercise, metabolites accumulate in the muscle interstitium where they stimulate chemosensitive afferent nerves that reflexly increase efferent muscle sympathetic nerve activity (MSNA) and blood pressure. In experimental animals, lactic acid potently stimulates the muscle metaboreflex, but its role in humans is more controversial. To determine if lactic acid is a critical mediator of metaboreflex activation in humans, we performed microelectrode recordings of MSNA in eight patients with myophosphorylase deficiency (McArdle's disease) who cannot metabolize intramuscular glycogen and do not generate lactic acid in exercising muscles. Each patient was matched with three healthy control subjects to maximize statistical power. In controls, 2 min of static handgrip performed at 33 % or 45 % of maximal voluntary contraction (MVC) produced intensity-dependent increases in MSNA (171 ± 22 % and 379 ± 95 %, respectively). In the patients, MSNA responses to static handgrip were markedly attenuated (33 ± 14 % at 33 % MVC; 32 ± 19 % at 45 % MVC; P < 0.05 vs. controls . Likewise, when static handgrip (30 % MVC) was performed to fatigue, MSNA increased by 366 ± 73 % in controls but only by 51 ± 14 % in patients (P < 0.05). Pressor responses to static handgrip were also attenuated in patients compared to controls, whereas heart rate responses were identical. In contrast to exercise, the MSNA responses to other reflex stimuli (the cold pressor test or Valsalva's manoeuvre) were similar in patients and controls. Together these data indicate that appropriate activation of glycogenolytic pathways is obligatory for normal metaboreflex-mediated sympathoexcitation during static exercise in humans.

AB - During static exercise, metabolites accumulate in the muscle interstitium where they stimulate chemosensitive afferent nerves that reflexly increase efferent muscle sympathetic nerve activity (MSNA) and blood pressure. In experimental animals, lactic acid potently stimulates the muscle metaboreflex, but its role in humans is more controversial. To determine if lactic acid is a critical mediator of metaboreflex activation in humans, we performed microelectrode recordings of MSNA in eight patients with myophosphorylase deficiency (McArdle's disease) who cannot metabolize intramuscular glycogen and do not generate lactic acid in exercising muscles. Each patient was matched with three healthy control subjects to maximize statistical power. In controls, 2 min of static handgrip performed at 33 % or 45 % of maximal voluntary contraction (MVC) produced intensity-dependent increases in MSNA (171 ± 22 % and 379 ± 95 %, respectively). In the patients, MSNA responses to static handgrip were markedly attenuated (33 ± 14 % at 33 % MVC; 32 ± 19 % at 45 % MVC; P < 0.05 vs. controls . Likewise, when static handgrip (30 % MVC) was performed to fatigue, MSNA increased by 366 ± 73 % in controls but only by 51 ± 14 % in patients (P < 0.05). Pressor responses to static handgrip were also attenuated in patients compared to controls, whereas heart rate responses were identical. In contrast to exercise, the MSNA responses to other reflex stimuli (the cold pressor test or Valsalva's manoeuvre) were similar in patients and controls. Together these data indicate that appropriate activation of glycogenolytic pathways is obligatory for normal metaboreflex-mediated sympathoexcitation during static exercise in humans.

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