Journal Article Review Epublish
PubMed: 40227402 DOI: 10.3390/antiox14030341
The Role of Hydrogen Sulfide in the Regulation of the Pulmonary Vasculature in Health and Disease.
Antioxidants (Basel) 14(3)
Authors: Philip I Aaronson
Affiliations
- Department of Inflammation Biology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London SE1 9RT, UK.
Abstract
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.
MeSH
Cells, Sulfides, Lung, Hypertension, Pulmonary, Pulmonary Artery, Sulfhydryl Compounds, Arteries, Hypoxia, Monocrotaline