It is well known that chronic inflammation is an important common pathway of various progressive kidney disease. It has also been reported that inflammasome activation, which is part of the innate immune system, plays an important role in such chronic inflammation. However, the mechanism involved in the prolongation of inflammasome activation is unknown. We focused on nitric oxide (NO) as a regulatory mechanism of inflammasome. To test the hypothesis that “Endothelial cells-induced nitric oxide inhibits inflammasome activation and regulates chronic inflammation,” we used wild-type (WT) and eNOS knockout (eNOSKO) mice.Design and Method:
 After unilateral nephrectomy (Nx), aldosterone (Ald) was continuously administered (0.25 mg/kg/day) using an infusion pump with 1% NaCl drinking water. The mice were sacrificed after 4 weeks of Ald administration, and the kidney tissue was examined.  We used bone-marrow-derived macrophages (BMDMs) to examine the molecular mechanism. After LPS priming (200 ng/mL 3 h), ATP (5 mM 60 min) was added to activate NLRP3 inflammasome. At the same time, we also performed priming with the NO donor, S-nitrosoglutathione (GSNO) to confirm the role of NO.Results:
 In the WT mice, administration of Ald-Nx-Nacl caused an increase in blood pressure, kidney tissue fibrosis and inflammasome activation. The eNOSKO mice showed a similar tendency, but the inflammation in kidney was even worse. Since blood pressure was higher in the eNOSKO mice, we administered hydralazine to both groups to lower the blood pressure to the same extent before the examination. Even when the blood pressure was lowered to the same extent, renal inflammasome activation was significantly enhanced in the eNOSKO mice.  BMDM stimulation with LPS-ATP caused NLRP3 inflammasome-dependent cell death and IL1beta secretion. GSNO inhibited this activation.Conclusions:
Endothelial cells-induced NO inhibits inflammasome activation to regulate chronic intrarenal inflammation. Endothelial dysfunction might promote chronic inflammation in CKD.