title: Role of glutamate and serotonin on the hypoxic ventilatory response in high-altitude-adapted plateau Pika.
abstract: The highland "plateau Pika" is considered to be adapted to chronic hypoxia. We hypothesized that glutamate N-methyl-D-aspartate (NMDA) and non-NMDA receptors, nitric oxide (NO) synthase, and serotonin are involved in hypoxic ventilatory response (HVR) in Pikas. We tested the effects of NMDA (memantine) and non-NMDA receptors (DNQX) antagonists, NO synthase inhibitor (L-NAME), and selective serotonin reuptake inhibitors (fluoxetine) on ventilation and HVR in Pikas. Ventilatory parameters were measured before and after drug (or vehicle) injections in conscious Pikas at their natural living altitude (PIO2 86 mmHg) and after a hypoxic challenge (PIO2 57 mmHg, 3 min) to assess the influence of peripheral chemoreceptor on HVR. Minute ventilation (VI) and tidal volume (Vt) increased during hypoxic challenge after vehicle injection, whereas the Ti/Ttot ratio remained unchanged. The increase in VI and Vt observed with vehicle at PIO2-57, when compared with PIO2-86, was inhibited after memantine and fluoxetine injection, whereas the DNQX injection increased HVR. At PIO2-57, L-NAME induced an increase in the Ti/Ttot ratio when compared with vehicle. Therefore, the glutamate through NMDA-R/AMPA receptor bindings and serotonin pathway are implicated at the peripheral chemoreceptor level in HVR in Pikas. However, NO influences the ventilatory pattern of Pikas at their habitual living altitude.
authors.affiliation: Research Centre for High Altitude Medicine, Qinghai University Medical College, Xining, Qinghai, PR China.
authors.forename: Zhenzhong
authors.initials: Z
authors.lastname: Bai
authors.affiliation: Université Paris 13, Sorbonne Paris Cité, Laboratoire "Hypoxie & Poumon" EA2363, Bobigny, France; Laboratory of Excellence GR-Ex, PRES Sorbonne Paris Cité, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Voituron
authors.affiliation: Research Centre for High Altitude Medicine, Qinghai University Medical College, Xining, Qinghai, PR China.
authors.forename: Tana
authors.initials: T
authors.lastname: Wuren
authors.affiliation: Université Paris 13, Sorbonne Paris Cité, Laboratoire "Hypoxie & Poumon" EA2363, Bobigny, France; Laboratory of Excellence GR-Ex, PRES Sorbonne Paris Cité, Paris, France.
authors.forename: Florine
authors.initials: F
authors.lastname: Jeton
authors.affiliation: Research Centre for High Altitude Medicine, Qinghai University Medical College, Xining, Qinghai, PR China.
authors.forename: Guoen
authors.initials: G
authors.lastname: Jin
authors.affiliation: Université Paris 13, Sorbonne Paris Cité, Laboratoire "Hypoxie & Poumon" EA2363, Bobigny, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Marchant
authors.affiliation: Université Paris 13, Sorbonne Paris Cité, Laboratoire "Hypoxie & Poumon" EA2363, Bobigny, France; Laboratory of Excellence GR-Ex, PRES Sorbonne Paris Cité, Paris, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Richalet
authors.affiliation: Research Centre for High Altitude Medicine, Qinghai University Medical College, Xining, Qinghai, PR China. Electronic address: geriligao@hotmail.com.
authors.forename: Ri-Li
authors.initials: RL
authors.lastname: Ge
authors.affiliation: Université Paris 13, Sorbonne Paris Cité, Laboratoire "Hypoxie & Poumon" EA2363, Bobigny, France; Laboratory of Excellence GR-Ex, PRES Sorbonne Paris Cité, Paris, France. Electronic address: aurelien.pichon@orange.fr.
authors.forename: Aurélien P
authors.initials: AP
authors.lastname: Pichon
mesh_terms: D000222:Adaptation, Physiological; D000531:Altitude; D000704:Analysis of Variance; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology*; D007793:Lagomorpha; D008297:Male; D008559:Memantine; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010991:Plethysmography; D012123:Pulmonary Ventilation / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology; D013990:Tidal Volume
chemical_list: D004791:Enzyme Inhibitors; D018683:Excitatory Amino Acid Agents; D018490:Serotonin Agents; D012701:Serotonin; D018698:Glutamic Acid; D019331:NG-Nitroarginine Methyl Ester; D008559:Memantine
keywords: Adaptation—control of breathing; Glutamate pathway; Hypoxia; Serotonin