Chronic social defeat stress promotes inflammation and severe hypertension in male mice
PHYSIOLOGY(2023)
Abstract
The worldwide prevalence of hypertension continues to rise, shortening lifespan and contributing to the risk of cardiovascular disease and stroke. Although there are numerous contributing risk factors, social adversity is believed to be one that may account, in part, for disparities in rates and treatment outcomes. We have recently begun to evaluate whether chronic social defeat stress (CSDS) can effectively model aspects of stress-induced cardiovascular disease. Adult male C57BL/6J mice were implanted with telemetry devices that recorded blood pressure, heart rate, core body temperature, and activity. Male CD1 mice were used to defeat C57BL/6J mice 1h before the onset of the dark cycle. Immediately following submission, the defeated mouse was housed in the same cage as the aggressor, physically separated by a perforated divider that allows for continuous visual, auditory, and olfactory contact. The C57BL/6J mouse was defeated and housed with a different CD1 mouse each day, to reduce the likelihood of habituation. Initial social defeat resulted in significant increases in blood pressure, activity, and temperature in comparison with control mice. Interestingly, while blood pressure returned to basal levels by the start of the light cycle for the first few days of defeat, chronic social defeat resulted in sustained elevations in blood pressure, lower activity and lower body temperature. Mice exposed to CSDS also exhibited anxiety-like behaviors, spending significantly more time in the closed arms of the elevated plus maze and less time in the center of an open field arena. At the end of the experiment, flow cytometry was performed on spleen and lung tissue from a subset of mice. Splenomegaly was observed in CSDS mice, with an increase in CD11b and monocytic and polymorphonuclear myeloid-derived suppressor cells (M-MDSCs and PMN-MDSCs), consistent with chronic inflammation. There were significant increases in PMN-MDSCs isolated from lung, a strong predictor of pulmonary hypertension, as well as enhanced immunosuppressive capability of MDSCs which is associated with the severity of disease. CSDS also resulted in increases in body, heart and adrenal weights and fluid retention. These data suggest that CSDS may be useful for modeling aspects of hypertension and immune dysfunction induced by chronic social stress, thereby enabling us to better understand the mechanisms that contribute to cardiovascular disease. R35HL150750 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
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Key words
chronic social defeat stress,male mice,severe hypertension
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