To elucidate whether by inhibiting inflammasome and oxidative stress, hydrogen sulfide (H2S) can ameliorate endothelial dysfunction with hypertension.
Spontaneously hypertensive rats (SHR) and normotensive Wistar–Kyoto rats (WKY) were injected with 100 μmol/l sodium hydrosulfide (NaHS) intraperitoneally daily for 16 weeks. SBP and plasma malondialdehyde (MDA) and interleukin 1β (IL-1β) levels were measured. Renal vascular function was used to determine endothelial-dependent contraction (EDC) and endothelial-dependent relaxation (EDR). Protein levels of NOX1, p67Phox, Nrf2, SOD1, CAT, NLRP3, caspase-1 and IL-1β were detected by western blot analysis. Human umbilical vein endothelial cells (HUVECs) were used to confirm the protective role of H2S against angiotensin II (Ang II)-induced cell injury.
Exogenous NaHS administration significantly reduced SBP and ameliorated damaged EDC and EDR. H2S reduced the activation of NLRP3 inflammasome and oxidative stress in SHR. The endothelial protective and antioxidant effect of H2S was abolished by lipopolysaccharide, an inducer of NLRP3 inflammasome. In HUVECs, H2S significantly ameliorated Ang II-induced cellular impairment, NLRP3 inflammasome activity and reactive oxygen species generation. After knocking down Nrf2, the protective effect of H2S was abolished.
H2S could inhibit the vicious cycle of oxidative stress and inflammation in hypertension, and then improve endothelial function and ameliorated hypertension. Our results help to reveal the crucial role of H2S in regulating endothelial function, which might be a new tool for treating hypertension.
aDepartment of Physiology, Institute of Basic Medicine, Hebei Medical University
bKey Laboratory of Vascular Medicine of Hebei Province
cHebei Collaborative Innovation Center for Cardio–cerebrovascular Disease
dHebei Key Lab of Laboratory Animal Science, Hebei Medical University, Shijiazhuang, China
Correspondence to Yuming Wu, No. 361 Zhongshan East Road, Shijiazhuang 050017, China. Tel: +86 311 86266407; fax: +86 311 86265619; e-mail: firstname.lastname@example.org
Abbreviations: Ang II, angiotensin II; CSE, cystathionine γ-lyase; EDC, endothelial-dependent contraction; EDR, endothelial-dependent relaxation; H2S, hydrogen sulfide; HUVECs, human umbilical vein endothelial cells; IL-1β, interleukin 1β; LPS, lipopolysaccharide; MDA, malondialdehyde; ROS, reactive oxygen species; SHR, spontaneously hypertensive rats; WKY, Wistar–Kyoto rats
Received 20 May, 2018
Revised 28 January, 2019
Accepted 5 March, 2019