Substance P receptor blockade decreases stretch-induced lung cytokines and lung injury in rats

Authors

  • Fabienne Brégeon,

    1. UMR MD2 P2COE, Institut Fédératif de Recherche Jean-Roche, Faculté de Médecine, Université de la Méditerranée Aix-Marseille II and Explorations Fonctionnelles Respiratoires de l’Hôpital Nord, Assistance Publique – Hôpitaux de Marseille, Marseille, France
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  • Jean Guillaume Steinberg,

    1. UMR MD2 P2COE, Institut Fédératif de Recherche Jean-Roche, Faculté de Médecine, Université de la Méditerranée Aix-Marseille II and Explorations Fonctionnelles Respiratoires de l’Hôpital Nord, Assistance Publique – Hôpitaux de Marseille, Marseille, France
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  • Nicolas Andreotti,

    1. ERT 62, ‘Ingénierie des Peptides à visée Thérapeutique’, Institut Fédératif de Recherche Jean-Roche, Université de la Méditerranée Aix-Marseille II, Marseille, France
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  • Jean-Marc Sabatier,

    1. ERT 62, ‘Ingénierie des Peptides à visée Thérapeutique’, Institut Fédératif de Recherche Jean-Roche, Université de la Méditerranée Aix-Marseille II, Marseille, France
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  • Stéphane Delpierre,

    1. UMR MD2 P2COE, Institut Fédératif de Recherche Jean-Roche, Faculté de Médecine, Université de la Méditerranée Aix-Marseille II and Explorations Fonctionnelles Respiratoires de l’Hôpital Nord, Assistance Publique – Hôpitaux de Marseille, Marseille, France
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  • Sylvie Ravailhe,

    1. UMR MD2 P2COE, Institut Fédératif de Recherche Jean-Roche, Faculté de Médecine, Université de la Méditerranée Aix-Marseille II and Explorations Fonctionnelles Respiratoires de l’Hôpital Nord, Assistance Publique – Hôpitaux de Marseille, Marseille, France
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  • Yves Jammes

    1. UMR MD2 P2COE, Institut Fédératif de Recherche Jean-Roche, Faculté de Médecine, Université de la Méditerranée Aix-Marseille II and Explorations Fonctionnelles Respiratoires de l’Hôpital Nord, Assistance Publique – Hôpitaux de Marseille, Marseille, France
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Corresponding author F. Brégeon: UMR MD2 P2COE, Faculté de Médecine Secteur Nord, Bd Pierre Dramard, 13916 Cedex 20, France. Email: fabienne.bregeon@ap-hm.fr

Abstract

Overdistension of lung tissue during mechanical ventilation causes cytokine release, which may be facilitated by the autonomic nervous system. We used mechanical ventilation to cause lung injury in rats, and studied how cervical section of the vagus nerve, or substance P (SP) antagonism, affected the injury. The effects of 40 or 25 cmH2O high airway pressure injurious ventilation (HV40 and HV25) were studied and compared with low airway pressure ventilation (LV) and spontaneous breathing (controls). Lung mechanics, lung weight, gas exchange, lung myeloperoxidase activity, lung concentrations of interleukin (IL)-1β and IL-6, and amounts of lung SP were measured. Control rats were intact, others were bivagotomized, and in some animals we administered the neurokinin-1 (NK-1) receptor blocking agent SR140333. We first determined the durations of HV40 and HV25 that induced the same levels of lung injury and increased lung contents of IL-1β and IL-6. They were 90 min and 120 min, respectively. Both HV40 and HV25 increased lung SP, IL-1β and IL-6 levels, these effects being markedly reduced by NK-1 receptor blockade. Bivagotomy reduced to a lesser extent the HV40- and HV25-induced increases in SP but significantly reduced cytokine production. Neither vagotomy nor NK-1 receptor blockade prevented HV40-induced lung injury but, in the HV25 group, they made it possible to maintain lung injury indices close to those measured in the LV group. This study suggests that both neuronal and extra-neuronal SP might be involved in ventilator-induced lung inflammation and injury. NK-1 receptor blockade could be a pharmacological tool to minimize some adverse effects of mechanical ventilation.

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