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GPER Contributes to the Development of Pulmonary Hypertension in Female Rats
Author(s) -
Ahmadian Rosstin,
Sheak Joshua R.,
Weise-Cross Laura,
Jernigan Nikki L.,
Arterburn Jeffrey B.,
Prossnitz Eric R.,
Snow Jessica B.,
Resta Thomas C.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.07087
Subject(s) - gper , pulmonary hypertension , medicine , endocrinology , estrogen receptor , hematocrit , right ventricular hypertrophy , estrogen , blood pressure , ventricular pressure , cardiology , cancer , breast cancer
Studies from our group and others demonstrate a protective role of estrogen in attenuating the progression of chronic hypoxia (CH)‐induced pulmonary hypertension. Physiological responses to estrogen are mediated by the nuclear estrogen receptors a and b, as well as by the membrane‐bound G protein‐coupled estrogen receptor (GPER). However, the role of GPER in the development of pulmonary hypertension resulting from CH is unknown. We hypothesized that GPER acts to limit the severity of CH‐induced pulmonary hypertension. To test this hypothesis, we evaluated indices of pulmonary hypertension in control and CH (4 wk, P B = 0.5 atm) female rats administered the GPER antagonist G36 via osmotic pumps (1 mg/kg/day, s.c.) during the entire 4 wk exposure period (n=7–8/group). Right ventricular systolic pressure (RVSP) was measured using a fluid‐filled catheter advanced through the right jugular vein into the right ventricle (RV) during isoflurane anesthesia. Additionally, RV hypertrophy was determined from Fulton’s index [RV/(LV+S)], and the polycythemic response to CH was assessed by measuring hematocrit. CH increased RVSP, Fulton’s Index, and hematocrit in vehicle‐treated rats (P<0.0001), indicative of pulmonary hypertension and associated polycythemia. Unexpectedly, RVSP was lower in G36‐treated CH rats compared to control animals (P<0.05), with a downward trending Fulton’s Index (not significant). However, hematocrit was unaltered by GPER inhibition. We conclude that GPER mediates a novel effect to facilitate the development of pulmonary hypertension resulting from CH exposure. Support or Funding Information NIH Grants R01 HL132883, T32 HL007736, and P20 GM103451. AHA Grant 18AIREA33960020