What question did this study set out to answer?

This research aims to determine if the GPER agonist G1 can mitigate hypertension and kidney dysfunction in a rat model mimicking post-menopausal women with sleep apnea.

May 14, 2026

GPER agonist G1 attenuates hypertension, renal hemodynamic dysregulation, and reductions in tissue oxygenation in ovariectomized rats conditioned with chronic intermittent hypoxia

Key Points

This research aims to determine if the GPER agonist G1 can mitigate hypertension and kidney dysfunction in a rat model mimicking post-menopausal women with sleep apnea.
Adult female Sprague Dawley rats were randomized into OVX and sham groups, then subjected to chronic intermittent hypoxia for 14 days.
G1 was administered via osmotic mini pumps, and mean arterial pressure, renal blood flow, and tissue oxygenation were measured.
Data were analyzed using ANOVA with Sidak Holm Multiple Comparison Tests.
OVX-CIH showed significantly higher MAP and lower RBF and PO2 compared to OVX alone.
In the OVX-CIH-G1 group, MAP was significantly lower and RBF and PO2 were significantly higher (p<0.05) compared to OVX-CIH.

Abstract

Introduction: Sleep apnea (SA) is recognized as an independent risk factor for development of hypertension (HTN) and chronic kidney disease (CKD). Epidemiological studies show HTN and CKD risk is lower in pre-menopausal women vs. men but increases after transition to menopause. Our lab has previously shown that estrogen loss in female rats via ovariectomy (OVX) combined with exposure to chronic intermittent hypoxia (CIH, an experimental model of SA) results in increased mean arterial pressure (MAP) and reductions in renal blood flow (RBF) and tissue oxygenation (PO 2 ). Other labs have shown that specific activation of the g-protein coupled estrogen receptor (GPER) attenuates increases in arterial pressure associated with OVX. Hypothesis: We hypothesized that activation of GPER with a selective agonist (G1) would attenuate previously observed increases in MAP and decreases in RBF and PO 2 in OVX females conditioned with CIH. Methods: Adult female Sprague Dawley rats were randomized to OVX/sham groups and then further randomized to CIH or AIR conditioning for 14 days while receiving treatment with G1 via osmotic mini pumps. MAP was measured non-invasively using tail cuff plethysmography and invasively using an indwelling arterial pressure catheter. RBF and PO 2 were measured under light isoflurane anesthesia (1.5-2% in air) under normoxic and hypoxic conditions. Data was analyzed using ANOVA w/ Sidak Holm Multiple Comparison Tests. Results: No significant differences were observed in MAP, RBF, or PO 2 between sham air and sham CIH groups, whereas MAP was higher and RBF and PO 2 lower in OVX-CIH vs. OVX groups. In the OVX-CIH-G1 group MAP was significantly lower and RBF and PO 2 were significantly higher (p< 0.05) relative to OVX-CIH. Conclusion: Our results suggest that ovarian hormone loss combined with CIH has a deleterious effect on regulation of MAP, RBF, and PO 2 that is attenuated by G1, suggesting an avenue for treatment of HTN and CKD in post-menopausal women with SA. Supported by a grant from the Iowa Osteopathic Education Research Fund (IOER #122205, #062503) and the DMU Mentored Student Research Program. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

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