抄録
It is well known that sheep can successfully inhabit highlands to an altitude, but not pig. We compared the effects of endogenous nitric oxide synthase (NOS) inhibition on pulmonary vascular tone in response to several hypoxic conditions in sheep and pig to evaluate the role of NO in adaptation to acute and chronic hypoxia. Unanaesthetized male sheep and pig in three areas; Matsumoto, Japan (680 m above sea level), Xing, China (2,300 m), and Maxin, China (3,750 m), were prepared for measurements of pulmonary artery (Ppa) and vascular resistance (PVR) before and after the NOS inhibition. The non-selective NOS inhibitor, Nw-nitro-L-argine (NLA, 20mg/kg) was used. Baseline Ppa became elevated with an increase in altitude in both animals. Ppa and PVR at baseline in pigs were significantly higher than those in sheep. The increase in PVR after NLA in sheep at 3,750 m was significantly higher than those in other groups, but there were no significant differences in three grade altitudes of pig. Furthermore, we examined the effects of acute hypoxic exposure from 2,300 m to 4,500 m in both animals using a hypobaric/hyperbaric controlled chamber with and without NLA. The enhanced pulmonary vasoconstriction after NO inhibition observed during hypoxic exposure in sheep but not pig. The increased endogenous NO production may contribute to regulating the pulmonary vascular tone in the adaptation to high-altitude in sheep. We conclude that NO plays a significant role in the pulmonary vascular tone in adaptable animal to hypoxia. [Jpn J Physiol 55 Suppl:S65 (2005)]
