Reactive oxygen species (ROS) produced following ischemic stroke damage vascular smooth muscle cells (SMCs) and endothelial cells (ECs) to a greater extent in males than females. Increases in mitochondrial calcium concentration (Ca 2 + m) promote cell death. As mitochondrial calcium uniporter (MCU) is the primary pathway for mitochondrial calcium uptake, we hypothesized that cerebral arteries from females have reduced MCU-dependent increases in Ca 2 + m during exposure to ROS, which limits cell death. Posterior cerebral arteries (PCAs; diameter ~80 μm) from mice were pressurized to 90 cm H 2 O (36°C) and exposed to hydrogen peroxide (H 2 O 2 , 200 μM) for 50 min. Cell death was evaluated with Hoechst 33342 (1 μM) to label all nuclei and propidium iodide (2 μM) to identify nuclei from dead cells. To assess the role of MCU, PCAs were treated with the MCU inhibitor DS16570511 (50 μM). MCU inhibition decreased SMC death in PCAs in males (26 to 5%; p< 0.05) but not females (15 to 10%) and decreased EC death in both sexes. Male PCAs had a significantly greater increase in Ca 2 + m in response to H 2 O 2 as measured by Rhod2 fluorescence (15 μM). Increases in Ca 2 + m were nearly abolished by MCU inhibition in both sexes. Activating MCU with kaempferol (15 μM; 30 min) led to a more robust increase in Ca 2 + m compared to H 2 O 2 , yet evoked minimal (~10%) SMC and EC death in both sexes. We concluded that greater resilience to oxidative stress in cerebral arteries from female mice is mediated by limiting mitochondrial calcium influx through MCU. Supported by: NIH R01NS134690. 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.
Elahi et al. (2026) studied this question.