Pharmacological inhibition of the NLRP3 inflammasome attenuates kidney apoptosis, fibrosis, and injury in Dahl salt-sensitive rats.

Abstract

Salt-sensitive hypertension (SSH) is the most severe form of hypertension, and the presence of NLRP3 inflammasome plays a crucial role in its pathogenesis. Although MCC950 has shown therapeutic potential for hypertension and kidney injury, its mechanism of action remains unclear. Dahl salt-sensitive (SS) rats and their salt-tolerant aptamer control SS-13BN (BN) rats were randomly assigned to four groups: SS rats intraperitoneally administered physiological saline (SS + vehicle) or MCC950 (SS + MCC950), and BN rats intraperitoneally administered physiological saline (BN + vehicle) or MCC950 (BN + MCC950). All rats were given 2% saline for drinking and received intraperitoneal injections of physiological saline or MCC950 (5mg/kg) every other day. Biomarkers such as serum creatinine, urinary protein, sodium retention, NLRP3 inflammasome, inflammation, apoptosis, fibrosis, sodium channels and histopathological changes in kidney injury were evaluated in blood, urine, and kidney tissues. Compared with the SS + vehicle group, the SS + MCC950 group showed significantly lower blood pressure levels. Additionally, inhibition of NLRP3 inflammasome activation was observed along with reduced inflammation, apoptosis, fibrosis, and sodium retention in the kidneys. The findings suggest that pharmacological inhibition of the NLRP3 inflammasome reduces blood pressure in SS rats and alleviates related kidney injury by suppressing inflammation, apoptosis, fibrosis, and sodium retention.