Role of G protein‐coupled estrogen receptors in pulmonary hypertension

Abstract

Chronic hypoxia (CH) resulting from chronic obstructive pulmonary disease, sleep apnea, and high altitude exposure leads to oxidative stress and increased pulmonary vascular resistance. The resultant pulmonary hypertension (PH) contributes to right ventricular hypertrophy and may culminate in right heart failure, peripheral edema, and dyspnea. Because the G protein‐coupled estrogen receptor (GPER) has been implicated in oxidative stress in systemic hypertension, we hypothesized that GPER contributes to the development of CH‐induced PH. To test this hypothesis, we assessed indices of PH in female wild type (WT) and GPER knockout (KO) mice exposed to normoxia or CH (4 wk, PB= 0.5 atm) (n= 4–6/group). Right ventricular systolic pressure (RVSP) was measured by direct cardiac puncture during isoflurane anesthesia. In addition, right ventricular hypertrophy and polycythemic responses to CH were determined from Fulton's index (right ventricle/(left ventricle + septum weight)) and hematocrit, respectively. CH resulted in greater RVSP in WT mice (p<0.05), indicative of PH. Although CH also tended to increase Fulton's index and hematocrit in WT mice, these responses did not reach statistical significance. GPER KO mice unexpectedly showed significantly (p < 0.05) elevated RVSP, right ventricular hypertrophy and hematocrit compared to WT controls under normoxic conditions. Furthermore, these responses to GPER knockdown were not potentiated by CH. We conclude that GPER deficiency results in PH under normoxic conditions, supporting a role for GPER in the maintenance of the pulmonary circulation as a low‐pressure circuit.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.