Electroacupuncture attenuates high-salt-induced hypertension by modulating neuronal excitability and proteomic signatures in the paraventricular nucleus of mice

Background High-salt-induced hypertension is associated with sympathetic overactivation, autonomic imbalance, and neurobehavioral abnormalities. The paraventricular nucleus (PVN) regulates autonomic output through projections to the rostral ventrolateral medulla (RVLM) and nucleus tractus solitarius (NTS). Although electroacupuncture (EA) has antihypertensive effects, its central mechanisms remain unclear. Mitochondrial dysfunction contributes to neurogenic hypertension, but the role of mitochondrial regulators such as adenine nucleotide translocator 1 (ANT1/SLC25A4) in PVN dysfunction remains unknown. Methods Male C57BL/6J mice were exposed to 2% NaCl for 4 weeks to induce hypertension, followed by EA stimulation at the Taichong (LR3) acupoint for 3 weeks. Blood pressure, behavioral performance, PVN neuronal activity, and molecular alterations were assessed using tail-cuff measurement, behavioral tests, retrograde tracing combined with whole-cell patch-clamp recording, and TMT-based quantitative proteomics, as well as using Western blotting and immunofluorescence analyses. Results High-salt exposure increased blood pressure and induced behavioral alterations. EA significantly reduced hypertension and improved behavioral abnormalities. High-salt exposure enhanced the intrinsic excitability of PVN–RVLM and PVN–NTS projection neurons, whereas EA normalized neuronal hyperactivity. Proteomic analysis revealed PVN remodeling involving mitochondrial oxidative phosphorylation, ATP/ADP transport, and transmembrane transport pathways. ANT1/SLC25A4 was downregulated in hypertensive mice but restored by EA, accompanied by reversal of inflammatory and stress-related protein alterations. Conclusions EA at LR3 reduced blood pressure and PVN neuronal hyperexcitability in mice with high-salt-induced hypertension. EA was also associated with normalization of mitochondrial-related proteomic changes and ANT1/SLC25A4 expression in the PVN. These findings identify ANT1-associated mitochondrial alterations as a potential molecular correlate of PVN dysfunction during EA treatment, but their causal contribution remains to be determined.