Hydrogen sulfide (H2S) is considered to be the third gasotransmitter after carbon monoxide (CO) and nitric oxide (NO). It plays an important role in the regulation of vascular homeostasis. Vascular remodeling have has proved to be related to the impaired H2S generation. This study aimed to summarize and discuss current data about the function of H2S in vascular physiology and pathophysiology as well as the underlying mechanisms. Endogenous hydrogen sulfide (H2S) as a third gasotransmitter is primarily generated by the enzymatic pathways and regulated by several metabolic pathways. H2S as a physiologic vascular regulator, inhibits proliferation, regulates its apoptosis and autophagy of vascular cells and controls the vascular tone. Accumulating evidence shows that the downregulation of H2S pathway is involved in the pathogenesis of a variety of vascular diseases, such as hypertension, atherosclerosis and pulmonary hypertension. Alternatively, H2S supplementation may greatly help to prevent the progression of the vascular diseases by regulating vascular tone, inhibiting vascular inflammation, protecting against oxidative stress and proliferation, and modulating vascular cell apoptosis, which has been verified in animal and cell experiments and even in the clinical investigation. Besides, H2S system and angiotensin-converting enzyme (ACE) inhibitors play a vital role in alleviating ischemic heart disease and left ventricular dysfunction. Notably, sulfhydryl-containing ACEI inhibitor zofenopril is superior to other ACE inhibitors due to its capability of H2S releasing, in addition to ACE inhibition. The design and application of novel H2S donors have significant clinical implications in the treatment of vascular-related diseases. However, further research regarding the role of H2S in vascular physiology and pathophysiology is required.

We examined the possible role of hydrogen sulfide (H₂S) in the pathogenesis of oleic acid (OA)-induced acute lung injury (ALI) and its regulatory effects on the inflammatory response. Compared to control rats, the OA-treated rats had decreased partial pressure of oxygen in the arterial blood (PaO₂) levels, an increased pulmonary wet/dry weight (W/D) ratio, increased index of quantitative assessment (IQA) score and increased frequency of polymorphonuclear (PMN) cells in the lung 2, 4 or 6 h after OA injection (0.1 ml/kg, intravenous injection). In addition, significantly increased IL-6, IL-8 and IL-10 levels together with decreased H₂S levels were observed in the plasma and lung tissue of OA-treated rats compared to controls. Administration of the H₂S donor sodium hydrosulfide (NaHS, 56 μmol/L, intraperitoneal injection) into OA-treated rats increased the PaO₂level, reduced the lung W/D ratio and infiltration of PMN cells, and alleviated the degree of ALI (measured by the IQA score). In addition, NaHS decreased IL-6 and IL-8 levels but increased IL-10 levels in the plasma and lung tissues, suggesting that H₂S may regulate the inflammatory response during ALI via regulation of IL-6, IL-8 and IL-10. Thus, the down-regulation of endogenous H₂S production might be involved in the pathogenesis of OA-induced ALI in rats.

Insulin resistance and impaired insulin secretion lead to disorders of glucose metabolism, which contributes to the development of diabetes. Hydrogen sulfide (H2S), a novel gasotransmitter, is found to play important roles in regulation of glucose metabolism homeostasis. This study aimed to summarize and discuss current data about the function of H2S in insulin secretion and insulin resistance regulation as well as the underlying mechanisms. H2S could be endogenously produced in islet β cells, liver, adipose, skeletal muscles, and the hypothalamus, and regulates local and systemic glucose metabolism. It is reported that H2S suppresses insulin secretion, promotes or reduces the apoptosis of islet β cells. It plays important roles in the regulation of insulin sensitivity in insulin responsive tissues. H2S inhibits glucose uptake and glycogen storage, and promotes or inhibits gluconeogenesis, mitochondrial biogenesis and mitochondrial bioenergetics in the liver. In adipose tissue, several investigators indicated that H2S promoted glucose uptake in adipocytes, while other studies reported that H2S inhibits this process. H2S has also been shown to promote adipogenesis, inhibit lipolysis, and regulate adiponectin and MCP-1 secretion from adipocytes. In skeletal muscle, H2S increases glucose uptake and improves insulin sensitivity. It is also observed that H2S modulates circadian-clock genes in muscle. Hypothalamic CBS/H2S pathway reduces obesity and improves insulin sensitivity via the brain-adipose interaction. Most studies indicated plasma H2S levels decreased in diabetic patients. However, the mechanisms by which H2S regulates systemic glucose metabolism remain unclear. Whether H2S acts as a new promising target for diabetes mellitus treatment merits further studies.