Gender differences in hypoxic vascular response of isolated sheep lungs

We compared the steady state stimulus-response relationship of the pulmonary circulation to graded hypoxia in isolated, in situ, blood-perfused lungs of postpubertal male and female sheep and male sheep of similar age that had been castrated within 1 wk of birth. The flow-resistive properties of the pulmonary circuit were assessed by pressure-flow curves generated over a wide range of flows (0-150 ml.min^-1.kg^-1 body wt^-1) at six different levels of inspired oxygen tension (PI(O₂)) between 200 and 0 Torr. The stimulus-response relationship was quantitated by determining the pulmonary arterial pressures at a flow of 50 ml.min^-1.kg^-1 (Ppa₅₀) directly from these curves. We found that this relationship was biphasic, as previously described for other species, with a peak vasoconstrictor response at a PI(O₂) = 30 Torr. The isolated lungs of males and castrated males achieved a greater maximal pressor response (Ppa₅₀ = 33 ± 3.7 and 34.5 ± 8 Torr, respectively) than did those of females (Ppa₅₀ = 20.2 ± 5.6 Torr, P < 0.01). When the pulmonary vascular bed was maximally dilated (PI(O₂) = 0 Torr), there were no significant differences in the Ppa₅₀ among the groups (Ppa₅₀ = 15.8 ± 4.6 in males, 11 ± 3.5 in females, and 11.5 ± 1.9 Torr in castrated males). There were no differences between males and castrated males at any PI(O₂). We conclude that the hypoxic pulmonary vasomotor response was attenuated in isolated lungs of postpubertal female sheep possibly due to the effect of female hormones.