Neuromuscular blocking agents block carotid body neuronal nicotinic acetylcholine receptors

Jonsson, Malin; Wyon, Nicholas; Lindahl, Sten G. E.; Fredholm, Bertil B.; Eriksson, Lars

doi:10.1016/j.ejphar.2004.06.052

Cited by 35 publications

(23 citation statements)

References 27 publications

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“…Our main result of a specific depression of HVR but not HCVR with partial neuromuscular blockade is consistent with previous work and as previously shown [8,9,[35][36][37][38]…”

Section: Discussionsupporting

confidence: 93%

Hypoxic ventilatory response after rocuronium‐induced partial neuromuscular blockade in men with obstructive sleep apnoea

et al. 2019

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Obstructive sleep apnoea and residual neuromuscular blockade are, independently, known to be risk factors for respiratory complications after major surgery. Residual effects of neuromuscular blocking agents are known to reduce the hypoxic ventilatory response in healthy volunteers. Patients with obstructive sleep apnoea have impaired control of breathing, but it is not known to what extent neuromuscular blocking agents interfere with the regulation of breathing in such patients. In a physiological study in 10 unsedated men with untreated obstructive sleep apnoea, we wished to examine if partial neuromuscular blockade had an effect on hypoxic ventilatory response (isocapnic hypoxia to oxygen saturation of 80%) and hypercapnic ventilatory response (normoxic inspired carbon dioxide 5%). The hypoxic ventilatory response was reduced by 32% (p = 0.016) during residual neuromuscular block (rocuronium to train-of-four ratio 0.7), but the hypercapnic ventilatory response was unaffected. We conclude that neuromuscular blockade specifically depresses peripheral chemosensitivity, and not respiratory muscle function since the hypercapnic ventilatory response was unaffected.

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“…Our main result of a specific depression of HVR but not HCVR with partial neuromuscular blockade is consistent with previous work and as previously shown [8,9,[35][36][37][38]…”

Section: Discussionsupporting

confidence: 93%

Hypoxic ventilatory response after rocuronium‐induced partial neuromuscular blockade in men with obstructive sleep apnoea

et al. 2019

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“…In contrast, if the rabbit carotid body is stimulated with nicotine there is a distinct dose‐dependent increase in carotid sinus nerve discharge frequency (Jonsson et al . ). As for ATP, its Ca 2+ ‐dependent release in response to hypoxia in several animal models has been established, as well as the key role for P2X signalling through studies on knockout mice (Zhang et al .…”

Section: Discussionmentioning

confidence: 97%

The human carotid body releases acetylcholine, ATP and cytokines during hypoxia

Kåhlin

Mkrtchian

Ebberyd

et al. 2014

Experimental Physiology

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New Findings r What is the central question of this study?Data on human carotid body (CB) function are limited. The aim of this study was therefore to investigate whether the human CB releases acetylcholine, ATP or cytokines during hypoxia. r What is the main finding and its importance?Using human CBs, we demonstrate hypoxia-induced acetylcholine and ATP release, suggesting that these neurotransmitters, as in several experimental animal models, play a role in hypoxic signalling also in the human carotid body. Moreover, the human CB releases cytokines upon hypoxia and expresses cytokine receptors as well as hypoxia-inducible factor proteins HIF-1α and HIF-2α in glomus cells, indicating their role in immune signalling and oxygen sensing, respectively, in accordance with previous animal data.Studies on experimental animals established that the carotid bodies are sensory organs for detecting arterial blood O 2 levels and that the ensuing chemosensory reflex is a major regulator of cardiorespiratory functions during hypoxia. However, little information is available on the human carotid body responses to hypoxia. The present study was performed on human carotid bodies obtained from surgical patients undergoing elective head and neck cancer surgery. Our results show that exposing carotid body slices to hypoxia for a period as brief as 5 min markedly facilitates the release of ACh and ATP. Furthermore, prolonged hypoxia for 1 h induces an increased release of interleukin (IL)-1β, IL-4, IL-6, IL-8 and IL-10. Immunohistochemical analysis revealed that type 1 cells of the human carotid body express an array of cytokine receptors as well as hypoxia-inducible factor-1α and hypoxia-inducible factor-2α. Taken together, these results demonstrate that ACh and ATP are released from the human carotid body in response to hypoxia, suggesting that these neurotransmitters, as in several experimental animal models, play a role in hypoxic signalling also in the human carotid body. The finding that the human carotid body releases cytokines in response to hypoxia adds to the growing body of information M.J.F. and L.I.E. contributed equally to this paper.

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“…Neuromuscular blocking agents, for example, vecuronium have been shown in humans to impair the HVR at concentrations where the patient's neuromuscular transmission is only slightly impaired and adequate enough to maintain protective airway reflexes, normal baseline ventilation, and ventilatory responses to hypercapnia (171)(172)(173). Subsequent in vitro experiments from the same institution using an isolated CB-sinus nerve preparation showed that neuromuscular blocking agents from different substance classes, that is, atracurium and vecuronium, impaired CB chemoreceptor activity through block of nACh receptors with an IC50 of 3.6 to 27 μM for atracurium and 1.6 to 7.3 μM for vecuronium depending on the nicotine concentration used to stimulate the CB nicotinic receptors (310). However, in humans the relevant ED90 plasma concentration for vecuronium that causes a 90% neuromuscular block has been reported to be 300 ng/mL (0.47 μM) (578) and the protein binding of vecuronium is reportedly 30% to 77% (153,183).…”

Section: Effects Of Neuromuscular Blocking Agents On the Peripheral Cmentioning

confidence: 97%

Effects of Anesthetics, Sedatives, and Opioids on Ventilatory Control

Stuth

Stucke

Zuperku

2012

Comprehensive Physiology

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This article provides a comprehensive, up to date summary of the effects of volatile, gaseous, and intravenous anesthetics and opioid agonists on ventilatory control. Emphasis is placed on data from human studies. Further mechanistic insights are provided by in vivo and in vitro data from other mammalian species. The focus is on the effects of clinically relevant agonist concentrations and studies using pharmacological, that is, supraclinical agonist concentrations are de-emphasized or excluded.

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Neuromuscular blocking agents block carotid body neuronal nicotinic acetylcholine receptors

Cited by 35 publications

References 27 publications

Hypoxic ventilatory response after rocuronium‐induced partial neuromuscular blockade in men with obstructive sleep apnoea

Hypoxic ventilatory response after rocuronium‐induced partial neuromuscular blockade in men with obstructive sleep apnoea

The human carotid body releases acetylcholine, ATP and cytokines during hypoxia

Effects of Anesthetics, Sedatives, and Opioids on Ventilatory Control

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