Effect of puberty and estradiol on hypoxic vasomotor response in isolated sheep lungs

We previously reported that in isolated lungs from 6-mo-old sheep acute hypoxia caused a greater vasoconstrictor response in males than in females but that this response in castrated males was not different from noncastrated males. To determine whether a gender difference exists before puberty, we compared the steady-state stimulus-response relationship of the pulmonary circulation to graded hypoxia in isolated perfused lungs of juvenile 2-mo-old male and female sheep. The flow-resistive properties of the pulmonary vessels were assessed by pressure-flow curves generated over a wide range of flows (0-150 ml X min-1 X kg-1) at six different levels of inspired O2 tension (PIO2) between 200 and 0 Torr. The stimulus-response relationship, quantified by plotting the pulmonary arterial pressure at a flow of 50 ml X min-1 X kg-1 against PIO2 was the same in juvenile male and female sheep lungs. Furthermore, the responses of juvenile sheep were not different from those of 6-mo-old males and were greater than those of 6-mo-old females. Treatment with 17 beta-estradiol (10-20 mg im) 2-5 days prior to perfusion significantly attenuated the response in the lungs from both 2-mo-old female and 6-mo-old castrated male sheep. We conclude that the gender difference in the hypoxic stimulus-response relationship observed in isolated lungs from 6-mo-old sheep arises from attenuation in the female at the time of puberty. This attenuation may be mediated by estradiol.