The effect of chronic unpredictable stress on renal mitochondrial function in female mice

Abstract

Background: Chronic stress can induce high blood pressure and lead to decreased renal function by mechanisms that remain unclear. The exposure of rodents to chronic unpredictable stress (CUS) is a translational model used for investigating the physiological impact of stress. The CUS protocol consists of unpredictable and random stressors that mimic real life exposure to stress. While stress is known to impact mitochondrial function, little is understood about the direct impact of chronic stress on renal mitochondrial respiration. Moreover, while studies have shown a link between estrogen and mitochondria through estrogen receptors, the relation between stress induced renal mitochondrial dysfunction and estrous cycle is unknown. Hypothesis: Exposing female mice to CUS will increase blood pressure and cause decreased renal mitochondrial respiration. Methods: We exposed adult female C57BL/6 mice to CUS for 28 days. Before and after stress, all control (CON, n=8) and CUS (n=10) mice were placed in metabolic cages for overnight urine collection. Urine albumin was measured by dipstick assay. On day 28, mice were assessed for blood pressure measurement via tail cuff. 24 hours later, mice were euthanized, and vaginal lavage was performed. The left kidney was removed, transected into thirds, and the poles were placed in relaxing buffer. Kidney mitochondrial oxygen consumption was assessed using high-resolution respirometry. Results: Data were stratified by phases of the estrus cycle. Neither blood pressure nor urinary albumin was significantly altered by CUS in stressed females. Females in estrus and proestrus exposed to CUS (n=5) exhibited a decrease of 20.8% ± 5.1 (n=5, p=0.03) in renal mitochondrial maximal uncoupled respiration compared to non-stressed CON. Renal mitochondrial respiration in diestrus was similar between CUS and CON. Conclusion: Results from this study reveal a link between the female estrus cycle, stress, and mitochondrial function. This work was supported by NIH grants P20GM109091 (F.H.), R01HL130972-01A1 (F.G.S.), R01HL5949 (F.G.S.), RO1DK132948 (C.W. & F.P.) and R01 MH129798 (SKW); VA grants: VISN7 RDA (F.H.), Merit awards: BX000168-10A1 (F.G.S.), BX005320 (F.G.S.), and BX002604 (M.J.R.). 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.