Blood pressure (BP) follows circadian rhythms regulated by clock genes, and disruption of BP rhythmicity increases cardiovascular disease risk. Estrogen regulates clock gene expression in central and peripheral tissues. We previously showed that hypertensive female mice exhibit blunted BP rhythms and disrupted expression of vascular clock genes. Estrogen receptors ERα and Gper1 display diurnal oscillations aligned with Per1 and Per2; however, these rhythms are disrupted in hypertension. Despite these observations, it remains unclear whether vascular circadian clock mechanisms contribute to BP dysregulation during estrogen loss. To test the hypothesis that estrogen loss disrupts BP rhythms and vascular clock gene regulation, we examined the effects of ovariectomy (OVX) on BP rhythms, as well as vascular clock gene and estrogen receptor expression. Female C57BL/6J mice were either intact or ovariectomized at 8 weeks of age and implanted with radiotelemetry devices. Six weeks after OVX, 24-hour BP was unchanged; however, OVX mice exhibited disrupted 12-hour BP rhythms and a non-dipping BP phenotype compared with intact controls (intact: 11 ± 0.7% vs. OVX: 7.8 ± 0.8%, P=0.01, N=5–6/group). In a separate cohort, aortas were collected during the light or dark phase for RNA sequencing and gene expression analysis by droplet digital PCR (ddPCR) of clock genes (Per1, Per2, Bmal1) and estrogen receptors (ERα, Gper1; N=8–12/group). In intact mice, Per1, Per2, and Bmal1 exhibited expected diurnal oscillations. Per1 expression was reduced during the light phase in OVX mice compared with intact controls (intact: 377 ± 49 vs. OVX: 258 ± 180 copies/ng, P=0.05), whereas Per2 and Bmal1 oscillations were not significantly altered by OVX. ERα and Gper1 exhibited diurnal oscillations in intact mice; however, only Gper1 expression was significantly reduced at dark phase in OVX mice (intact 40 ± 12 vs 24 ± 49 copies/ng, P=0.01). RNA sequencing pathway analysis demonstrated diurnal regulation of clock gene expression in intact mice euthanized during the light and dark phases, as expected. In contrast, OVX mice exhibited reduced expression of core circadian genes during the light phase, including Period genes, Cry2, Rora, DBP, and casein kinase 1 isoforms (CK1ε and CK1δ). Light–dark comparisons in OVX mice also revealed altered expression of pathways related to smooth muscle contraction, vascular contractile genes, and collagen organization. In conclusion, estrogen loss disrupts BP rhythms and promotes a non-dipping BP phenotype, accompanied by diurnal dysregulation of vascular circadian gene expression and Gper1 expression in ovariectomized female mice. These findings indicate that OVX disrupts circadian regulation of vascular clock and contractile gene expression and impairs diurnal regulation of vascular tone, which may contribute to disrupted BP rhythms. Future studies will examine the impact of estrogen replacement and aging on BP and vascular clock genes, with a focus on estrogen receptors as potential modulators. Funding: NIH-NIGMS (P20GM152305) and Sleep Research Society. 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.
Visniauskas et al. (Fri,) studied this question.