Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a wide variety of hepatic disorders and is a leading cause of cirrhosis and hepatocellular carcinoma. Sleep apnea (SA) is believed to contribute to development of MASLD by primary liver damage, and secondary factors including hypertension (HTN). Both MASLD and SA prevalence are significantly higher in postmenopausal women vs. pre-menopausal women, suggesting estrogen loss may play a role in SA/MASLD pathophysiology. In support of this notion, activation of the G protein coupled estrogen receptor (GPER1) with a specific agonist (G1) has been shown to protect against MASLD development in female mice. G1 has also been shown to prevent increases in mean arterial pressure (MAP) in ovariectomized (OVX) rats. Reduced hepatic perfusion and related tissue hypoxia are hypothesized to play a role in MASLD pathophysiology, with HTN acting as a potentially modifying factor. To date, no studies have addressed the intersection of sex steroid hormones and SA in the context of HTN, MASLD, and SA. Hypothesis: Loss of sex steroid hormones in females via OVX combined with chronic intermittent hypoxia (CIH, a model of SA) will result increased MAP and lower hepatic tissue PO2 (HPO2), and these changes will be attenuated by treatment with G1. Methods: Adult female Sprague Dawley rats (n=6-8 per group) were randomized to OVX or sham groups and were implanted with osmotic mini-pumps containing G1 (400 μg/kg/day). Rats were then further randomized to CIH or control (sham) conditioning for 8h/d for 14 days. MAP was measured non-invasively using tail cuff plethysmography and invasively using an indwelling arterial pressure catheter. HPO2 was measured using fiber optic probes (Oxford Optronics) under anesthesia during FiO2 0.21 and FiO2 0.10. Data was analyzed using ANOVA w/ Sidak Holm Multiple Comparison Tests. Results: No significant differences were observed in MAP between sham air and sham CIH groups, whereas MAP was higher and HPO2 lower in OVX-CIH vs. CIH. In the OVX-CIH-G1 group MAP was significantly lower (p< 0.05) relative to OVX-CIH. Reductions in HPO2 in response to FiO2 0.10 were greater in CIH-OVX vs. CIH (p< 0.05), an effect that was attenuated by G1 treatment (p< 0.05). Conclusion: Our findings that CIH conditioning promotes HTN and accentuates tissue hypoxia in OVX females suggests that SA combined with hormone loss may play a role in MASLD development or progression in post-menopausal women. Supported by grants 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.
Watson et al. (Fri,) studied this question.