Chronic Stress Alters The Supraspinal Control of Blood Pressure

Cardiovascular disease is the number one cause of morbidity and mortality in the United States, accounting for 695,000 deaths in 2021 alone (CDC, 2024). Blood pressure homeostasis relies on rapid vasomotor regulation arising from a variety of brain regions, as well as slower neurohumoral regulation of blood volume via the kidneys. Dysfunction of these homeostatic mechanisms can significantly contribute to cardiovascular disease. The medial prefrontal cortex (MPFC) has been implicated in top-down feedforward vasomotor control of blood pressure and general cardiovascular outflow. Dysregulated MPFC activity has also been implicated in models of chronic stress and cardiovascular disease. While MPFC stimulation elicits mean arterial pressure (MAP) depressor responses, researchers have not yet characterized the full extent of cardiovascular responses produced from stimulation including cortical depressor area and response magnitude. Along with defining evoked responses in more detail, there is currently a limited understanding of whether chronic stress drives neural plasticity in the MPFC altering blood pressure regulation. Thus, this study seeks to use a chronic stress model to explore the vasomotor regulation of blood pressure through electrophysiological assessment of the MPFC, as well as a neuroanatomical assessment of kidney innervation from subcortical and cortical structures. In the first experiment, male Wistar rats (n=7) were either mapped as controls or exposed to 28 days of restraint stress and subsequently mapped across the full MPFC unilaterally using intracortical microstimulation. Behavioral and neuroendocrine responses to stress were assessed using elevated plus maze, open field, and plasma biomarkers. We note significant increases in both MAP depressor response area (Independent 2 tailed t-test, p = 0.019, d = 1.44) and MAP depressor response magnitude (Mann-Whitney U test, p = 0.026, d = 1.37) in the chronic stress group compared to controls. Together these conclusions support the hypothesis that chronic stress causes neural plasticity in the MPFC by expanding the cortical area dedicated to buffering increases in MAP occurring during restraint stress. To assess neurohumoral control of the kidney, animals were exposed to the same chronic stress model and subsequently injected with the retrograde transsynaptic tracer PRV-152 into the kidney to assess subcortical and cortical connectivity. Together, these experiments explore multiple critical substrates of blood pressure control crucial for understanding the impact of stress and cardiovascular dysfunction. This study was supported by: NIH (R01 NS131493) This abstract was presented at the American Physiology Summit 2025 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.