Activation of G Protein‐Coupled Estrogen Receptor 1, with a GPER Agonist, Reduces Blood Pressure in Female Growth‐Restricted Rats in Later Life

Abstract

The prevalence of hypertension (HTN) is two‐fold higher in low birth weight (LBW) women at age 60 relative to their normal birth weight (NBW) counterparts. Yet, the mechanisms that contribute to greater cardiovascular risk in LBW women are not known. In our model of intrauterine growth restriction (IUGR), induced by placental insufficiency in the pregnant rat, female IUGR offspring have an elevated blood pressure (BP) at 12 months of age that is associated with early reproductive senescence. Although estrogen levels do not differ between control and IUGR groups, there is a significant increase in testosterone levels in female IUGR that is not seen in female control. Elevated testosterone levels, due to an imbalance in the hormonal milieu, is suggested to contribute to the development of hypertension in women in later life. We previously reported that chronic administration of estradiol is able to abolish the increase in blood pressure in the female IUGR rat at 12 months of age. However, this was not accomplished through alterations in expression of the nuclear estrogen receptor alpha (ER‐alpha). In the current study, we tested the hypothesis that activation of G protein‐coupled estrogen receptor 1 (GPER) would reduce blood pressure in the female IUGR rat. The selective GPER agonist, G1 (400 g/kg/day), or vehicle was administered via osmotic pumps for 2 weeks beginning at 14 months of age. BP was measured in conscious, chronically catheterized rats following treatment (2way ANOVA; Tukey's multiple comparison). As shown previously, BP was significantly elevated in vehicle‐treated IUGR relative to vehicle‐treated control (138.3± 4.01 vs. 124.3 ± 0.70mmHG, respectively). BP was significantly decreased in G1‐treated IUGR relative to vehicle‐treated IUGR (125.14±4.03 vs. 138.3 ± 4.01mmHG, respectively), whereas BP was not significantly altered in G1‐treated control relative to vehicle‐treated control (124.5 ± 0.66 vs. 124.3 ± 0.70mmHG, respectively). Uterine weight did not differ between groups. Therefore, this data suggests that activation of GPER was able to abolish the increase in blood pressure in the female IUGR rat in later life. This study suggests that GPER may serve as a therapeutic target for ameliorating increases in blood pressure seen in LBW women in later life.Support or Funding InformationNIH: R56HL143459, P20GM121334, P20GM104357, P01‐HL51971, T32HL105324, F30DK112718. AHA: GRNT19900004, PRE34060010.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.