PMID- 24744892 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20140418 LR - 20211021 IS - 2051-817X (Print) IS - 2051-817X (Electronic) IS - 2051-817X (Linking) VI - 2 IP - 2 DP - 2014 Feb 1 TI - Catalyzing role of erythropoietin on the nitric oxide central pathway during the ventilatory responses to hypoxia. PG - e00223 LID - 10.1002/phy2.223 [doi] LID - e00223 AB - The N-Methyl-d-Aspartate (NMDA) receptors - neuronal nitric oxide synthase (nNOS) pathway is involved in the ventilatory response to hypoxia. The objective was to assess the possible effect of erythropoietin deficiency and chronic exposure to hypoxia on this pathway during ventilatory response to acute hypoxia. Wild-type (WT) and erythropoietin-deficient (Epo-TAg(h)) male mice were exposed (14 days) either to hypobaric hypoxia (Pb = 435 mmHg) or to normoxia. The ventilation was measured at 21% or 8% O2 after injection of vehicle (NaCl), nNOS inhibitor (SMTC) or NMDA receptor antagonist (MK-801). Nitric oxide production and the expression of NMDA receptor and nNOS were assessed by real-time RT-PCR and Western blot analyses in the medulla. At rest, Epo-TAg(h) mice displayed normal ventilatory parameters at 21% O2 but did not respond to acute hypoxia despite a larger expression of NMDA receptors and nNOS in the medulla. Ventilatory acclimatization to hypoxia was observed in WT but was absent in Epo-TAg(h) mice. nNOS inhibition blunted the hypoxic ventilatory acclimatization of WT mice without any effect in Epo-TAg(h) mice. Acute hypoxic ventilatory response (HVR) was increased after chronic hypoxia in WT but remained unchanged in Epo-TAg(h) mice. Ventilatory response to acute hypoxia was modified by MK-801 injection in WT and Epo-TAg(h) mice. The results confirm that adequate erythropoietin level is necessary to obtain an appropriate HVR and a significant ventilatory acclimatization to hypoxia. Furthermore, erythropoietin plays a potential catalyzing role in the NMDA-NO central pathway during the ventilatory response and acclimatization to hypoxia. FAU - Voituron, Nicolas AU - Voituron N AD - Laboratoire "Reponses cellulaires et fonctionnelles a l'hypoxie", Universite Paris 13, Sorbonne Paris Cite, UFR SMBH, EA 2363, Bobigny, 93017, France ; Laboratory of Excellence (Labex) GR-Ex, PRES Sorbonne Paris Cite. FAU - Jeton, Florine AU - Jeton F AD - Laboratoire "Reponses cellulaires et fonctionnelles a l'hypoxie", Universite Paris 13, Sorbonne Paris Cite, UFR SMBH, EA 2363, Bobigny, 93017, France ; Laboratory of Excellence (Labex) GR-Ex, PRES Sorbonne Paris Cite. FAU - Cholley, Yannick AU - Cholley Y AD - Laboratoire "Reponses cellulaires et fonctionnelles a l'hypoxie", Universite Paris 13, Sorbonne Paris Cite, UFR SMBH, EA 2363, Bobigny, 93017, France. FAU - Hasnaoui-Saadani, Raja El AU - Hasnaoui-Saadani RE AD - Laboratoire "Reponses cellulaires et fonctionnelles a l'hypoxie", Universite Paris 13, Sorbonne Paris Cite, UFR SMBH, EA 2363, Bobigny, 93017, France. FAU - Marchant, Dominique AU - Marchant D AD - Laboratoire "Reponses cellulaires et fonctionnelles a l'hypoxie", Universite Paris 13, Sorbonne Paris Cite, UFR SMBH, EA 2363, Bobigny, 93017, France. FAU - Quidu, Patricia AU - Quidu P AD - Laboratoire "Reponses cellulaires et fonctionnelles a l'hypoxie", Universite Paris 13, Sorbonne Paris Cite, UFR SMBH, EA 2363, Bobigny, 93017, France. FAU - Favret, Fabrice AU - Favret F AD - Laboratoire "Reponses cellulaires et fonctionnelles a l'hypoxie", Universite Paris 13, Sorbonne Paris Cite, UFR SMBH, EA 2363, Bobigny, 93017, France. FAU - Richalet, Jean-Paul AU - Richalet JP AD - Laboratoire "Reponses cellulaires et fonctionnelles a l'hypoxie", Universite Paris 13, Sorbonne Paris Cite, UFR SMBH, EA 2363, Bobigny, 93017, France ; Laboratory of Excellence (Labex) GR-Ex, PRES Sorbonne Paris Cite. FAU - Pichon, Aurelien AU - Pichon A AD - Laboratoire "Reponses cellulaires et fonctionnelles a l'hypoxie", Universite Paris 13, Sorbonne Paris Cite, UFR SMBH, EA 2363, Bobigny, 93017, France ; Laboratory of Excellence (Labex) GR-Ex, PRES Sorbonne Paris Cite. LA - eng PT - Journal Article DEP - 20140214 PL - United States TA - Physiol Rep JT - Physiological reports JID - 101607800 PMC - PMC3966246 OTO - NOTNLM OT - Erythropoietin OT - NMDA receptors OT - hypoxia EDAT- 2014/04/20 06:00 MHDA- 2014/04/20 06:01 PMCR- 2014/02/14 CRDT- 2014/04/19 06:00 PHST- 2013/10/30 00:00 [received] PHST- 2014/01/09 00:00 [revised] PHST- 2014/01/11 00:00 [accepted] PHST- 2014/04/19 06:00 [entrez] PHST- 2014/04/20 06:00 [pubmed] PHST- 2014/04/20 06:01 [medline] PHST- 2014/02/14 00:00 [pmc-release] AID - phy2223 [pii] AID - 10.1002/phy2.223 [doi] PST - epublish SO - Physiol Rep. 2014 Feb 14;2(2):e00223. doi: 10.1002/phy2.223. eCollection 2014 Feb 1.