Abstract: TH-PO0130
Electrical Vagal Nerve Stimulation (eVNS) Reduces Kidney Sympathetic Nerve Activity and Protects Kidneys from Ischemia-Reperfusion Injury (IRI) in Mice
Session Information
- AKI: Mechanisms - 1
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Mohammed, Mazher, Icahn School of Medicine at Mount Sinai, New York, New York, United States
- Lazartigues, Eric D., LSU Health New Orleans, New Orleans, Louisiana, United States
- Padanilam, Babu J., Icahn School of Medicine at Mount Sinai, New York, New York, United States
Background
Electrical vagus nerve stimulation (eVNS) has emerged as a promising therapeutic strategy with multifaceted protective effects. Recent studies demonstrate that eVNS exerts its benefits partly through activation of the cholinergic anti-inflammatory pathway, particularly via splenic modulation and suppression of proinflammatory cytokines such as TNF-α and IL-6—key mediators of renal injury (Niemann, 2021). In this study, we investigated whether eVNS reduces renal sympathetic nerve activity (RSNA) and protects against acute kidney injury induced by ischemia-reperfusion injury (IRI) in mice.
Methods
Anesthetized mice underwent eVNS at varying frequencies (1, 2, 5, and 10 Hz) while RSNA, blood pressure (BP), and heart rate (HR) were simultaneously recorded. In a separate cohort, mice recovered from eVNS and underwent assessments of glomerular filtration rate (GFR), baseline RSNA, BP, and HR. To induce renal IRI, mice were subjected to 30 minutes of bilateral renal artery occlusion. Renal injury was assessed via GFR measurements and histological analysis of fibrosis in kidneys from IRI-only and eVNS+IRI groups.
Results
eVNS significantly reduced RSNA, BP, and HR in a frequency-dependent manner (RSNA: R2 = 0.827; BP: R2 = 0.667; HR: R2 = 0.494; n = 6, p < 0.01 for all). Intermittent stimulation at 10 Hz (5s ON/OFF for 10 min) led to sustained reductions in baseline RSNA and attenuated the sympathetic response to IRI (n = 6, p < 0.05). Pre-treatment with 10 min of intermittent eVNS one day prior to IRI significantly preserved kidney function, as evidenced by improved GFR, compared to IRI-alone controls (n = 5, p < 0.05). Histological analysis revealed markedly reduced kidney fibrosis in the eVNS+IRI group (p < 0.05) at 10 days post-injury.
Conclusion
These findings demonstrate that eVNS mitigates renal injury following IRI, through suppression of RSNA and, modulation of peripheral cholinergic anti-inflammatory pathways. Elucidating the central mechanisms underlying eVNS-induced sympathoinhibition may offer novel therapeutic avenues for the treatment of acute and chronic kidney disease.
Funding
- NIDDK Support