Pristane-induced lupus elevates blood pressure and superimposed chronic stress causes renal and cardiac hypertrophy

Background and Hypothesis: Hypertension has autoimmune origins, and chronic stress is associated with hypertension and immune system activation. Patients with autoimmune diseases like systemic lupus erythematosus (SLE) have prevalent hypertension, renal injury, and cardiovascular disease. SLE disproportionately affects young women and clinical evidence suggests that stress can trigger disease flares. The underlying mechanisms of stress-induced exacerbation of autoimmune disease and associated hypertension are unknown. The present study subjected female mice with SLE to a chronic unpredictable stress (CUS) protocol to test the hypothesis that chronic stress will exacerbate hypertension in a female mouse model of SLE. Methods and Results: Eight-week old female C57BL/6 mice were administered a single injection (0.5mL, i.p.) of either pristane (Acros Organics) to induce SLE, or saline (vehicle). Starting at 14 weeks of age mice were randomly assigned to either non-stressed group-housed control (CON) or single-housed stressed (CUS) groups (n=8/group) until 30 weeks of age. At week 14, CUS animals were exposed to 28 days of daily CUS designed to mimic unpredictability of stress in daily life while CON mice were handled gently weekly for 28 days. In the 3 days following the protocol, anhedonic-like (sucrose splash test), avoidant (open field) and coping style (forced swim test) behaviors were assessed. Only the forced swim test showed an overall effect of CUS to decrease latency to immobility (in seconds, 71± 13 vs 43±1 CON vs CUS, p=0.02). At 29 weeks of age, tail cuff blood pressure (Visitech) was assessed after 3 previous days of training. Systolic pressure was higher in pristane treated animals (in mmHg, 140±3 vs 152±1 saline vs pristane, p=0.06), though there was no statistical effect of stress on pressure. At 30 weeks of age, mice were euthanized, tissues were collected and weighed, and normalized to tibia length (mg/cm). Spleen and thymus weights were significantly higher in pristane treated animals (42±0.2 vs 52±1.3 and 29±1 vs 39±2 saline vs pristane, p=0.03) but this was not impacted by CUS. Adrenal weight was increased in CUS mice (3.2±0.1 vs 3.9±0.2 CON vs CUS, p< 0.01), with a significant increase in adrenal weight in pristane CUS compared to pristane CON (3.2±0.2 vs 3.9±0.3 pristane CON vs pristane CUS, p=0.03). Both renal and heart weight were increased in CUS animals (83±3 vs 96±3 and 67±2 vs 74±3 CON vs CUS, p< 0.01), with a statistical increase in the pristane CUS animals (80±4 vs 99±3 and 65±2 vs 76±2, pristane CON vs pristane CUS, p< 0.02). Conclusion: These data suggest that CUS induces a passive coping style in female mice, and that mice treated with pristane have increased blood pressure. Furthermore, this study supports the potential interaction of chronic stress and autoimmunity to drive renal and cardiac hypertrophy. This work was supported by U54HL169191 and BX002604 to MJR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the abstract. 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.