ReviewThe biological effect of endogenous sulfur dioxide in the cardiovascular system
Introduction
Sulfur dioxide (SO2) is considered a toxic gas in air pollution and detrimental to many organs. Its toxicological effects have been extensively investigated (Meng, 2003, Meng and Bai, 2004). However, SO2 can be generated endogenously during normal amino acid metabolism in mammals (Stipanuk, 1986). Using a Gas ChromatographyāMass Spectrometry method, Balazy et al. (2003) analyzed headspace gas carbonyl sulfide (COS) and SO2 in vascular tissue and found that COS and SO2 levels could be increased by acetylcholine and the calcium ionophore (A23187) in vascular tissue. Additionally, SO2 can originate from the unstable gas, sulfur monoxide (SO), and may be a candidate for the unknown substance, endothelium-derived hyperpolarizing factor (Balazy et al., 2003). Nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factor are believed to be three endothelium-derived relaxing factors (Feletou and Vanhoutte, 2006). Nitric oxide and prostacyclin production was abolished in mice following the knockout of endothelial nitric oxide synthase (eNOS) and cyclooxygenase-1, however, the endothelium-dependent relaxing effect was still present (Scotland et al., 2005). Endothelium-derived hyperpolarizing factor might play a compensatory role, whereas nitric oxide and prostacyclin production is inhibited under pathological conditions. Thus, endothelium-derived hyperpolarizing factor may be responsible for vascular tone regulation.
SO2 dissociates to its derivatives (bisulfite and sulfite [NaHSO3/Na2SO3], 1:3Ā M/M, in neutral fluid and plasma) in mammals (Shapiro, 1977). Our understanding of the biological effect of Du et al. first discovered cardiovascular endogenous SO2 is very limited in mammals. In contrast to its toxic effect, endogenous SO2/aspartate aminotransferase pathway and found that it has important physiological and pathophysiological effects in the cardiovascular system at physiological concentrations (Du et al., 2008, Jin et al., 2008). The reference range for total serum sulfite (SO2 derivative) is 0ā10Ā Ī¼M in healthy donors (Ji et al., 1995). The sulfite concentration is tightly regulated to maintain homeostasis in humans. In patients with acute pneumonia and renal failures, serum sulfite was significantly increased (Kajiyama et al., 2000, Mitsuhashi et al., 2004). This article mainly reviews the biological effects of the gas mediator, SO2, on the cardiovascular system. The evidence suggests that SO2 may be a potential gasotransmitter in mammals.
Section snippets
Metabolism of endogenous SO2
Endogenous SO2 can be produced from sulfur-containing amino acids such as l-cysteine in mammals. l-cysteine is oxidized via cysteine dioxygenase to l-cysteine sulfinate, which converts to Ī²-sulfinylpyruvate through transamination by aspartate aminotransferase, and finally spontaneously decomposes to pyruvate and SO2 (Shapiro, 1977, Stipanuk et al., 1990). In addition, H2S can be oxidized via sulfide oxidase to thiosulfate, and then converted to sulfite by thiosulfate sulfurtransferase or
Endothelium-dependent vasorelaxation induced by SO2
The vasorelaxing effect of SO2 is endothelium-dependent at low concentrations and endothelium-independent at high concentrations (Meng et al., 2009). Both SO2 and its derivatives have a vasorelaxing effect, however, this effect and its underlying mechanisms differ (TableĀ 1) (Du et al., 2008, Meng et al., 2009). Studies (Du et al., 2008, Zhang and Meng, 2009) have shown that the median effective concentration required to induce a 50% effect (EC50) on the vasodilation induced by SO2 and its
Anti-hypertensive effect of SO2
Zhao et al. (2008a) reported that SO2 content and aspartate aminotransferase activity in serum and the aorta were lower in male spontaneously hypertensive rats, however, blood pressure, the ratio of wall thickness to lumen radius and the proliferation index of the aorta were increased. A similar effect was also found in WKY rats following hydroxamate (an inhibitor of endogenous sulfur dioxide generation) treatment (Zhao et al., 2008a). In spontaneously hypertensive rats treated with SO2,
Perspectives and challenges
Gasotransmitters have the following characteristics, (a) a small molecular gas can freely diffuse through biological membranes; (b) they can be generated endogenously and the generation can be regulated; (c) at physiological concentrations, they have special biological functions. For example, NO and carbon monoxide (CO) both have a regulatory effect on vascular tone; (d) they have specific biological targets whether they are mediated or not by second messengers (Pun et al., 2010, Wang, 2002).
SO2
Acknowledgment
This work was supported by Major Basic Research Program of China (, ), the National Natural Science Foundation of China (, ), the Changjiang Scholar Program, and grants from the Ministry of Education, China (, ).
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