Lungs from chronically hypoxic rats have decreased pressor response to acute hypoxia

We measured pressor responses in blood-perfused lungs from rats kept at low altitude (LA, 1,520 m) and from rats exposed to simulated high altitude (HA, 4-6 wk at 4,270 m) to see if lungs from chronically hypoxic rats were hyper- or hyporeactive to acute airway hypoxia. HA lungs had bigger pressor responses to intra-arterial angiotensin II, prostaglandin F2alpha, and norepinephrine, but smaller responses to airway hypoxia than did LA lungs. The dose-response curve to hypoxia in HA lungs was shifted to the right of that in LA lungs. Thus, HA lungs were hyperreactive to intra-arterial agonists, but were hyporeactive to acute airway hypoxia. In contrast, additional experiments with rats that had been exposed to HA for 5 wk and then returned to LA for 3 days showed that the lungs from such post-HA rats were hyperreactive to acute airway hypoxia. The decreased pressor responsiveness to acute hypoxia in lungs from chronically hypoxic rats could have been due to an increased activity of some endogenous vasodilator or to some abnormality in the mechanism that couples hypoxia to contraction of the vascular smooth muscle.