Hydrogen sulfide suppresses angiotensin II-stimulated endothelin-1 generation and subsequent cytotoxicity-induced endoplasmic reticulum stress in endothelial cells via NF-κB.

The effects of hydrogen sulfide (H2S) and the nuclear factor κB (NF-κB) signaling pathway in angiotensin II (AngII)-induced endothelin-1 (ET-1) expression and subsequent cytotoxicity remain unclear. The present study aimed to investigate the hypothesis that H2S protects human umbilical vein endothelial cells (HUVECs) against AngII‑stimulated ET‑1 generation and subsequent cytotoxicity‑induced endoplasmic reticulum stress via the NF‑κB signaling pathway. The results of the present study demonstrated that AngII significantly upregulated the expression levels of ET‑1, glucose‑regulated protein 78, CCAAT‑enhancer‑binding protein homologous protein, phosphorylated (p)‑p65 and inducible nitric oxide synthase; stimulated nitric oxide production; suppressed the expression and activity of cystathionine-γ-lyase (CSE), a H2S synthetase; and decreased cell viability. Conversely, BQ788 (an ET‑1 receptor antagonist) exhibited an inhibitory effect on the AngII‑mediated suppression of CSE expression and activity in HUVECs. The effects of AngII were abrogated by sodium hydrosulfide (NaHS, an H2S donor), BQ788 or pyrrolidinedithiocarbamic acid (PDTC, an inhibitor of NF‑κB). Furthermore, pretreatment with NaHS or PDTC attenuated AngII‑induced apoptosis and cleaved caspase-12 generation. The pretreatment of HUVECs with BQ788 prior to AngII exposure mimicked the inhibitory effect of NaHS on the expression of p‑p65 induced by AngII. In conclusion, the present study provides evidence that exogenous H-2S attenuates AngII‑induced inflammation and cytotoxicity via inhibition of the ET‑1/NF‑κB signaling pathway in HUVECs.