Effects of hydrogen sulphide on oxidative stress, inflammatory cytokines, and vascular remodelling in l‐NAME‐induced hypertension

Abstract

This study was designed to evaluate the protective effects of hydrogen sulphide (H2S) against NG‐Nitro l‐Arginine Methyl Ester (l‐NAME)‐induced hypertension and its possible effects on the inflammatory process, oxidative stress, and vascular remodelling in rats. Forty male Wistar Albino rats were assigned to four equal groups: the control group, the H2S control group, the hypertensive group, and the treated group, which received concomitant treatment with sodium hydrosulphide (NaHS) and l‐NAME. Systolic blood pressure (SBP) was measured weekly. Serum levels of nitric oxide (NO), total peroxide, and total antioxidant capacity (TAC) were measured and the oxidative stress index (OSI) was calculated. Aortic weight and length were measured and the aortic weight/length ratio determined. Aortic fold expression of interferon‐γ (IFN‐γ) and vascular cell adhesion molecule‐1 (VCAM‐1) mRNA was measured using qPCR. Aortic media thickness and elastin content were measured morphometrically. l‐NAME administration increased SBP, serum levels of total peroxide and OSI, but reduced serum levels of NO and TAC. Aortic fold expression of IFN‐γ and VCAM‐1 mRNA, aortic weight, aortic weight/length ratio, aortic media thickness, and elastin area percentage were increased in the hypertensive group. Concurrent administration of l‐NAME and H2S attenuated these changes. Thus, H2S could attenuate the increase in ABP through restoration of the NO level, reduction in the oxidative state, and attenuation of the inflammatory process, thereby reduced vascular remodelling.

Sodium Thiosulphate-Loaded Liposomes Control Hydrogen Sulphide Release and Retain Its Biological Properties in Hypoxia-like Environment

“…As previously established, the limited availability of oxygen during hypoxia forces cells to rely on less efficient metabolic routes such as glycolysis for ATP production [ 47 , 48 ]. Nonetheless, previous reports in our laboratory and others suggest that H 2 S donors enhance mitochondrial bioenergetics [ 37 , 46 , 87 ] and modulate anti-oxidant [ 87 ] and anti-inflammatory processes in the vascular system [ 26 , 40 , 88 , 89 ], potentially by acting as an electron donor to the electron transport chain [ 90 ]. Figure 5 and Figure 6 highlight that non-encapsulated and liposome formulated STS significantly enhanced rates of mitochondrial respiration in cells challenged with hypoxia.…”

Hydrogen Sulfide: An Emerging Precision Strategy for Gas Therapy

“…Although a large number of studies have reported the regulatory role of H 2 S in both pro-and anti-inflammatory processes, the mechanistic insights of H 2 S in inflammatory processes are still unclear. [154][155][156][157] Zanardo et al reported that H 2 S can induce neutrophil apoptosis and inhibit the expression of some leukocytes and endothelial adhesion molecules by activating K ATP channels to suppress endogenous H 2 S production and elicit leukocyte adherence. [158] Ekundi-Valentim et al reported that exogenous H 2 S achieved a prominent anti-inflammatory and antinociceptive effect when delivered to the knee joint, while H 2 S produced in situ exerted weak immunomodulatory effect.…”

“…[213] In summary, although the intrinsic mechanism of H 2 S antioxidant defense response is disputable, it is possible that the production and bioavailability of H 2 S can directly regulate cellular redox status for antioxidant effect. [154,155,214]…”