Role of glutamate and serotonin on the hypoxic ventilatory response in high-altitude-adapted plateau Pika

The highland plateau Pika is considered to be adapted to chronic hypoxia. We hypothesized that glutamate N-methyl-o-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 (P1O2 86 mmHg) and after a hypoxic challenge (13102 57 mmHg, 3 min) to assess the influence of peripheral chemoreceptor on HVR. Minute ventilation (VI) and tidal volume (V-t) increased during hypoxic challenge after vehicle injection, whereas the T-i/T-tot ratio remained unchanged. The increase in VI and Vt observed with vehicle at P1O2-57, when compared with P1O2-86, was inhibited after memantine and fluoxetine injection, whereas the DNQX injection increased HVR. At P1O2-57, L-NAME induced an increase in the T-i/T-tot 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. (C) 2015 Elsevier B.V. All rights reserved.