N-Acetylcysteine reduces hyperacute intermittent hypoxia-induced sympathoexcitation in human subjects

Noah P. Jouett, Gilbert Moralez, Daniel W. White, Wendy L. Eubank, Shande Chen, Jun Tian, Michael L. Smith, Matthew C. Zimmerman, Peter B. Raven

Research output: Contribution to journalArticle

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Abstract

This investigation tested the following hypotheses: that (i) N-acetylcysteine (N-AC) attenuates hyperacute intermittent hypoxia-induced sympathoexcitation, (ii) without elevating superoxide measured in peripheral venous blood. Twenty-eight healthy human subjects were recruited to the study. One hour before experimentation, each subject randomly ingested either 70 mg kg-1 of N-AC (n = 16) or vehicle placebo (n = 12). Three-lead ECG and arterial blood pressure, muscle sympathetic nerve activity (n = 17) and whole-blood superoxide concentration (using electron paramagnetic resonance spectroscopy; n = 12) were measured. Subjects underwent a 20 min hyperacute intermittent hypoxia training (hAIHT) protocol that consisted of cyclical end-expiratory apnoeas with 100% nitrogen. N-AC decreased muscle sympathetic nerve activity after hAIHT compared with placebo (P < 0.02). However, N-AC did not alter superoxide concentrations in venous blood compared with placebo (P > 0.05). Moreover, hAIHT did not increase superoxide concentrations in the peripheral circulation as measured by electron paramagnetic resonance (P > 0.05). Based on these findings, we contend that (i) hAIHT and (ii) the actions of N-AC in hAIHT are primarily mediated centrally rather than peripherally, although central measurements of reactive oxygen species are difficult to obtain in human subjects, thus making this assertion difficult to verify. This investigation suggests the possibility of developing a pharmaceutical therapy to inhibit the sympathoexcitation associated with obstructive sleep apnoea.

Original languageEnglish
Pages (from-to)387-396
Number of pages10
JournalExperimental physiology
Volume101
Issue number3
DOIs
StatePublished - 1 Mar 2016

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Acetylcysteine
Superoxides
Electron Spin Resonance Spectroscopy
Placebos
Muscles
Obstructive Sleep Apnea
Apnea
Hypoxia
Reactive Oxygen Species
Spectrum Analysis
Healthy Volunteers
Arterial Pressure
Electrocardiography
Nitrogen
Pharmaceutical Preparations

Cite this

Jouett, N. P., Moralez, G., White, D. W., Eubank, W. L., Chen, S., Tian, J., ... Raven, P. B. (2016). N-Acetylcysteine reduces hyperacute intermittent hypoxia-induced sympathoexcitation in human subjects. Experimental physiology, 101(3), 387-396. https://doi.org/10.1113/EP085546
Jouett, Noah P. ; Moralez, Gilbert ; White, Daniel W. ; Eubank, Wendy L. ; Chen, Shande ; Tian, Jun ; Smith, Michael L. ; Zimmerman, Matthew C. ; Raven, Peter B. / N-Acetylcysteine reduces hyperacute intermittent hypoxia-induced sympathoexcitation in human subjects. In: Experimental physiology. 2016 ; Vol. 101, No. 3. pp. 387-396.
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Jouett, NP, Moralez, G, White, DW, Eubank, WL, Chen, S, Tian, J, Smith, ML, Zimmerman, MC & Raven, PB 2016, 'N-Acetylcysteine reduces hyperacute intermittent hypoxia-induced sympathoexcitation in human subjects', Experimental physiology, vol. 101, no. 3, pp. 387-396. https://doi.org/10.1113/EP085546

N-Acetylcysteine reduces hyperacute intermittent hypoxia-induced sympathoexcitation in human subjects. / Jouett, Noah P.; Moralez, Gilbert; White, Daniel W.; Eubank, Wendy L.; Chen, Shande; Tian, Jun; Smith, Michael L.; Zimmerman, Matthew C.; Raven, Peter B.

In: Experimental physiology, Vol. 101, No. 3, 01.03.2016, p. 387-396.

Research output: Contribution to journalArticle

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