Long-term ventilatory adaptation and ventilatory response to hypoxia in plateau pika (Ochotona curzoniae): role of nNOS and dopamine.
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 (Vi) was measured using a whole body plethysmograph in conscious pikas (n = 9) and low-altitude (LA) rats (n = 7) at different Pi(O(2)) (56, 80, 111, 150, and 186 mmHg) and in HA acclimatized rats (n = 9, 8 days at 4,600 m) at two different Pi(O(2)) (56 and 80 mmHg). The effects of NaCl, SMTC, and haloperidol on ventilatory patterns were assessed in pikas at Pi(O(2)) = 56 and 80 mmHg. We observed a main species effect with larger Vi, 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 Vi and VT for a Pi(O(2)) of 56 mmHg, but had no effect for a PiO(2) 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.
Pichon
Aurélien
A
Laboratoire Réponses Cellulaires et Fonctionnelles à l'Hypoxie, Université Paris 13, Bobigny, France. aurelien.pichon@orange.fr
Zhenzhong
Bai
B
Favret
Fabrice
F
Jin
Guoen
G
Shufeng
Han
H
Marchant
Dominique
D
Richalet
Jean-Paul
JP
Ge
Ri-Li
RL
D000064:Acclimatization; D000818:Animals; D002956:Citrulline / Q000031:analogs & derivatives / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D045853:Exhalation; D006220:Haloperidol / Q000494:pharmacology; D000860:Hypoxia / Q000201:enzymology / Q000503:physiopathology*; D001239:Inhalation; D007793:Lagomorpha; D008297:Male; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012123:Pulmonary Ventilation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015656:Respiratory Mechanics / Q000187:drug effects; D013045:Species Specificity; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D013990:Tidal Volume; D013997:Time Factors
D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D002956:Citrulline; D052248:Nitric Oxide Synthase Type I; D013890:Thiourea; D006220:Haloperidol; C086717:S-methylthiocitrulline; D004298:Dopamine