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Articles

Long-term ventilatory adaptation and ventilatory response to hypoxia in plateau pika (Ochotona curzoniae): role of nNOS and dopamine

¹Université Paris 13, Laboratoire "Réponses cellulaires et fonctionnelles à l'hypoxie," Bobigny, France; and ²Qinghai University Medical College, Research Centre for High Altitude Medicine, Xining, Qinghai, R. P. China

Submitted February 17, 2009 ; accepted in final form July 23, 2009

We assessed ventilatory patterns and ventilatory responses to hypoxia (HVR) in high-altitude (HA) plateau pikas, repetitively exposed to hypoxic burrows, and control rats. We evaluated the role of neuronal nitric oxide synthase (nNOS) and dopamine by using S-methyl-L-thiocitrulline (SMTC) inhibitor and haloperidol antagonist, respectively. Ventilation (I) was measured using a whole body plethysmograph in conscious pikas (n = 9) and low-altitude (LA) rats (n = 7) at different PI_O2 (56, 80, 111, 150, and 186 mmHg) and in HA acclimatized rats (n = 9, 8 days at 4,600 m) at two different PI_O2 (56 and 80 mmHg). The effects of NaCl, SMTC, and haloperidol on ventilatory patterns were assessed in pikas at PI_O2 = 56 and 80 mmHg. We observed a main species effect with larger I, tidal volume (VT), inspiratory time/total time (T_i/T_tot), and a lower expiratory time in pikas than in LA rats. Pikas had also a larger VT and lower respiratory frequency compared with HA rats in hypoxia. HVR of pikas and rats were not statistically different. In pikas, SMTC induced a significant increase in I and VT for a PI_O2 of 56 mmHg, but had no effect for a PIO₂ of 80 mmHg, i.e., the living altitude of pikas. In pikas, haloperidol injection had no effect on any ventilatory parameter. Long-term ventilatory adaptation in pikas is mainly due to an improvement in respiratory pattern (VT and T_i/T_tot) with no significant improvement in HVR. The sensitivity to severe acute hypoxia in pikas seems to be regulated by a peripheral nNOS mechanism.

adaptation; control of breathing; dopamine