Does H2S in the paraventricular nucleus improve spontaneous hypertension by regulating the PERK/TXNIP/NLRP3 pathway?
H2S in the paraventricular nucleus exerts anti-inflammatory protective effects and improves spontaneous hypertension by inhibiting the PERK/TXNIP/NLRP3 pathway.
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.
Liang et al. (Wed,) studied this question.