Aaronson Philip I
Department of Inflammation Biology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London SE1 9RT, UK.
Antioxidants (Basel). 2025 Mar 14;14(3):341. doi: 10.3390/antiox14030341.
The gasotransmitter hydrogen sulfide (HS; also termed sulfide) generally acts as a vasodilator in the systemic vasculature but causes a paradoxical constriction of pulmonary arteries (PAs). In light of evidence that a fall in the partial pressure in oxygen (pO) increases cellular sulfide levels, it was proposed that a rise in sulfide in pulmonary artery smooth muscle cells (PASMCs) is responsible for hypoxic pulmonary vasoconstriction, the contraction of PAs which develops rapidly in lung regions undergoing alveolar hypoxia. In contrast, pulmonary hypertension (PH), a sustained elevation of pulmonary artery pressure (PAP) which can develop in the presence of a diverse array of pathological stimuli, including chronic hypoxia, is associated with a decrease in the expression of sulfide -producing enzymes in PASMCs and a corresponding fall in sulfide production by the lung. Evidence that PAP in animal models of PH can be lowered by administration of exogenous sulfide has led to an interest in using sulfide-donating agents for treating this condition in humans. Notably, intracellular HS exists in equilibrium with other sulfur-containing species such as polysulfides and persulfides, and it is these reactive sulfur species which are thought to mediate most of its effects on cells through persulfidation of cysteine thiols on proteins, leading to changes in function in a manner similar to thiol oxidation by reactive oxygen species. This review sets out what is currently known about the mechanisms by which HS and related sulfur species exert their actions on pulmonary vascular tone, both acutely and chronically, and discusses the potential of sulfide-releasing drugs as treatments for the different types of PH which arise in humans.
气体信号分子硫化氢（HS，也称为硫化物）在体循环血管系统中一般起血管舒张作用，但却会引起肺动脉（PA）的反常收缩。鉴于有证据表明氧分压（pO）下降会使细胞内硫化物水平升高，有人提出肺动脉平滑肌细胞（PASMCs）内硫化物水平升高是低氧性肺血管收缩的原因，低氧性肺血管收缩是指在经历肺泡低氧的肺区域迅速发生的肺动脉收缩。相比之下，肺动脉高压（PH）是指肺动脉压力（PAP）持续升高，在包括慢性低氧在内的多种病理刺激下都可能发生，它与PASMCs中产生硫化物的酶表达减少以及肺内硫化物生成相应下降有关。有证据表明，在PH动物模型中，给予外源性硫化物可降低PAP，这引发了人们对使用供硫剂治疗人类这种疾病的兴趣。值得注意的是，细胞内HS与多硫化物和过硫化物等其他含硫物质处于平衡状态，正是这些活性硫物质被认为通过蛋白质上半胱氨酸硫醇的过硫化作用介导了其对细胞的大部分影响，从而导致功能发生类似于活性氧对硫醇氧化的变化。这篇综述阐述了目前已知的HS及相关硫物质对肺血管张力急性和慢性作用机制方面的知识，并讨论了供硫药物作为治疗人类出现的不同类型PH的潜力。
