Mechanism of paraventricular nucleus H2S on PERK/TXNIP/NLRP3 pathway in male spontaneously hypertensive rats

  • Physiol Rep. 2026 Apr;14(7):e70861. doi: 10.14814/phy2.70861.
Yan-Feng Liang  1  2  3 ,  Shu-Yue Chen  1 ,  Hui Wang  1 ,  Han-Jun Song  1 ,  Bao-Cheng Zhang  1 ,  Ming-Fu Wang  1 ,  Chao Lv  1 ,  Xiao-Yu Wang  1 ,  Shuai Zhang  1 ,  Huai-Yu Xing  1  4 ,  Quan Yuan  1 ,  Hong-Bin Li  1 ,  Xin-Rui Ding  1 ,  Zhang-Ran Xing  1 ,  Xin-Yi Han  1 ,  Dong-Dong Zhang  1  2  3
Affiliations
  • 1. School of Basic Medicine, Jiamusi University, Jiamusi, China.
  • 2. Key Laboratory of Microecology-Immune Regulatory Network and Related Diseases School of Basic Medicine, Jiamusi University, Jiamusi, China.
  • 3. Provincial Demonstration Center for Experimental Teaching of Basic Medicine, Jiamusi University, Jiamusi, China.
  • 4. School of Rehabilitation Medicine, Jiamusi University, Jiamusi, China.
PMID: 41964264 DOI: 10.14814/phy2.70861
Abstract

Hydrogen sulfide (H2S) exhibits anti-inflammatory, anti-apoptotic, and antioxidant effects. However, the central nervous system regulatory mechanisms of H2S in hypertension remain unclear. This study aimed to investigate the regulatory effects of H2S on the PERK/TXNIP/NLRP3 pathway and the paraventricular nucleus (PVN) inflammatory responses by injecting S-adenosylmethionine (SAMe, an endogenous H2S agonist) or the PERK Inhibitor GSK2606414 (GSK) into the PVN of spontaneously hypertensive rats (SHR). Additionally, we employed a lipopolysaccharide (LPS)-induced cell inflammation model and intervened with SAMe or the NLRP3 Activator BMS-986299 (BMS) to further validate the relevant molecular mechanisms. Relevant indicators were analyzed using tail artery blood pressure measurement, CCK-8 assay, ELISA, immunofluorescence, western blot, and real-time quantitative polymerase chain reaction (RT-qPCR). This study found that H2S in the PVN improves spontaneous hypertension by inhibiting the PERK/TXNIP/NLRP3 pathway and reducing sympathetic activity. Cell experiments further confirmed that the inhibitory effect of H2S on this pathway is the key mechanism underlying its anti-inflammatory protective effects.

Keywords
PERK/TXNIP/NLRP3; hydrogen sulfide; hypertension; paraventricular nucleus; pro‐inflammatory cytokines.
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