1766 EFFECTS OF 17β ESTRADIOL ON THE PULMONARY CIRCULATION

Abstract

Prior studies have shown that 1) mature ewes have an attenuated hypoxic pulmonary vasoconstrictor response (HPVR), 2) 17β estradiol (E2) administered 2-4 days prior to study of juvenile ewes reduces their HPVR to adult ewe levels, 3) E2 enhances prostaglandin production by systemic vessels. This study examined the effects of indomethacin (I) on the steady state pulmonary vascular response to graded hypoxia in isolated perfused lungs of 3 groups of juvenile ewes - controls (C and CI), E2 treated 36-60 hours before study (E2S, E2SI) and E2 treated 72-110 hours before study (E2L, E2LI). Mean pulmonary artery pressure (Ppa) at flow = 50 ml/kg·min for 3 levels of inspired O2 (PiO2) for each group (n) were: (* = less than C, p<.05).In all groups the peak response is seen at 30 torr. There was a time dependent attenuation of the HPVR caused by E2. While indomethacin had no effect on the HPVR in any group, it did return responsivity (Δ in Ppa 200→30) in E2L to C values (p<.05). These results suggest that although E2 may increase pulmonary prostaglandin synthesis, there is also an apparent time-dependent reduction in vascular resistance caused by non-prostaglandin dependent mechanisms.