S'abonner

Facilitation of the respiratory rhythm in mice by acute exposure to a progestin, the etonogestrel. Involvement of medullary areas - 04/04/15

Doi : 10.1016/j.rmr.2015.02.085 
F. Joubert , A.S. Perrin-Terrin, M.N. Fiamma, P. Cardot, A. Frugiere, L. Bodineau
 UMR_S1158 Inserm, Université Pierre-et-Marie-Curie, Neurophysiologie Respiratoire Expérimentale et Clinique - Physiologie et Plasticité du Contrôle Respiratoire, France 

Corresponding author.

Bienvenue sur EM-consulte, la référence des professionnels de santé.
Article gratuit.

Connectez-vous pour en bénéficier!

Résumé

Background

Works have underlined the facilitatory influence of progestins on central respiratory drive (CRD). The congenital central hypoventilation syndrome (CCHS) is a neuro-respiratory disease characterized by an alteration of the CO2/H+ chemosensitivity due to dysfunction of CO2/H+ chemosensitive/PHOX2b-positive neurons of the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG). In our laboratory, a recovery of the CO2/H+ chemosensitivity was fortuitously observed in two CCHS women who took a potent synthetic progestin, the desogestrel (Respir Physiol Neurobiol 2010;171:171–4).

Objective

Our aim was to appreciate the effects of an acute exposure to etonogestrel (ETO), the main active metabolite of the desogestrel, on the CRD and to determine its medullary action mechanisms.

Methods

We used:

– an analysis of the effect of ETO (0.05–2μM) on the CRD of ex vivo medullary-spinal cord preparations from newborn mice in both normopH and metabolic acidosis;

– pharmacological co-application of ETO and muscimol or NMDA, agonists of GABAA or NMDA receptors known to be a target of some steroids;

– an analysis of the c-fos expression in medullary respiratory structures.

Results

First, the respiratory frequency was:

– dose-dependently increased in normopH by ETO (≈+23–47%; P<0.01) in comparison to control preparations exposed to DMSO, (solvent of ETO);

– increase by metabolic acidosis similarly under ETO (≈+28–37% at 0.05–1μM, P<0.05 and P<0.001, respectively) and DMSO (≈+40%; P<0.001).

Second, changes in respiratory frequency induced by muscimol or NMDA at their EC50 were more potent under ETO (≈−60–63%, P<0.001 and ≈+53±65%, P<0.001 respectively) than under DMSO (≈−33%, P<0.01 and +29%, P<0.05, respectively). Finally, analysis of c-fos revealed ETO activated cells in respiratory medullary areas i.e. the ventrolateral medulla, nucleus of the solitary tract, RTN/pFRG and medullary raphe nuclei.

Conclusions

As a whole, data suggest that, by medullary mechanisms, the progestin ETO exerts a facilitatory influence on the CRD by acting at the level of respiratory structures. Involved mechanisms would implicate an interaction with GABAA and NMDA receptors. Besides, at least in newborn mice, ETO do not potentiate the respiratory response to metabolic acidosis by intrinsic medullary mechanisms.

Le texte complet de cet article est disponible en PDF.

Keywords : Physiology, Ventilatory control


Plan


© 2015  Publié par Elsevier Masson SAS.
Imprimer
Export

    Export citations

  • Fichier

  • Contenu

Vol 32 - N° 3

P. 339 - mars 2015 Retour au numéro
Article précédent Article précédent
  • Syndrome d’Ondine : tentative de traitement sur un modèle murin par le 17-AAG
  • J. Pautrat, I. Gaigher, M. Ringot, B. Matrot, A. Denjean, J. Gallego, N. Ramanantsoa
| Article suivant Article suivant
  • Enhancement of the respiratory response to acidosis in newborn rat by a progestin, involvement of diencephalic areas
  • C. Loiseau, D. Osinski, C. Lavaysse, L. Bodineau