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 D. Thomas

Research output: Contribution to journalReview articlepeer-review

35 Scopus citations


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
Issue number3
StatePublished - May 1 2003

All Science Journal Classification (ASJC) codes

  • Physiology


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