Probiotics regulate blood pressure and improve cardiovascular health in chronic stress rats through oxidative stress reduction

Introduction: Chronic stress adversely impacts the cardiovascular system, partly by inducing gut dysbiosis, contributing to cardiovascular diseases. Probiotics, known for their antioxidant properties, may modulate pathways like SIRT1 activation, improving endothelial function and reducing oxidative stress. Objective: This study aimed to test whether probiotic treatment reduces oxidative stress, modulates SIRT1 expression and positively influences blood pressure in chronic stress. Methods: Male Wistar rats (n=8/group) were assigned to Control (C), Stress (S), Control+Probiotic (CP), and Stress+Probiotic (SP) groups. Probiotics ( Lacticaseibacillus rhamnosus and Limosilactobacillus reuteri, 1 billion CFU/probiotics, Terapêutica Farmácia de Manipulação, Brazil) were administered for 8 weeks. Chronic mild and unpredictable stress (CMUS - protocol #6533240621) was applied during weeks 3–5. Blood pressure was measured by plethysmography, and biochemical analyses were conducted using commercial kits. Results: The CUMS protocol induced stress, increasing corticosterone levels (S: 206.4 ± 150 vs. C: 60.8 ± 34 ng/mL, p<0.05), mitigated by probiotics (SP: 59.2 ± 75.7 ng/mL, p<0.05). Stress increased insulin levels (S: 68.5 ± 18 vs. C: 41 ± 18.5 pg/mL, p<0.05; SP: 79.2 ± 25 vs. CP: 41 ± 12 pg/mL, p<0.05), CK levels (S: 17.02 ± 6.59 vs. C: 7.29 ± 3.28; SP: 9.88 ± 1.99 U/L), and SIRT1 expression (S: 1.02 ± 0.2 vs. C: 0.64 ± 0.13 2- ΔΔCT ), effects reversed by probiotics, except by SIRT1. Probiotics also increased antioxidant enzyme activity (SOD1: SP: 57.41 ± 1.32 vs. S: 52.48 ± 1.27%, p<0.05; Catalase: SP: 23603 ± 5868 vs. S: 5045 ± 193.7 mIU/mL, p<0.05) and altered gut microbiota, increasing Lactobacillus (SP: 24.6% vs. S: 18.41%) and Prevotellaceae_NK3B31_group (SP: 12.71% vs. S: 10.82%). The biochemical changes observed were accompanied by functional alterations, with probiotic reducing mean blood pressure (SP:83±9 vs. S:123±8 mmHg). Conclusion: Probiotics positively impacted oxidative stress markers and regulated blood pressure in rats under chronic stress, effects that appear to be not mediated by SIRT1 modulation. Additionally, probiotics altered gut microbiota composition. Collectively, our findings suggest that probiotics may serve as a complementary strategy for managing cardiovascular risk associated with chronic stress. Funding: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) [grant number 2021/05331-1 and 2017/17027-0]. 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.