Hydrogen Sulfide Metabolism and Pulmonary Hypertension

Pulmonary hypertension (PH) is a severe and multifactorial disease characterized by a progressive elevation of pulmonary arterial resistance and pressure due to remodeling, inflammation, oxidative stress, and vasoreactive alterations of pulmonary arteries (PAs). Currently, the etiology of these pathological features is not clearly understood and, therefore, no curative treatment is available. Since the 1990s, hydrogen sulfide (H₂S) has been described as the third gasotransmitter with plethoric regulatory functions in cardiovascular tissues, especially in pulmonary circulation. Alteration in H₂S biogenesis has been associated with the hallmarks of PH. H₂S is also involved in pulmonary vascular cell homeostasis via the regulation of hypoxia response and mitochondrial bioenergetics, which are critical phenomena affected during the development of PH. In addition, H₂S modulates ATP-sensitive K⁺ channel (K_ATP) activity, and is associated with PA relaxation. In vitro or in vivo H₂S supplementation exerts antioxidative and anti-inflammatory properties, and reduces PA remodeling. Altogether, current findings suggest that H₂S promotes protective effects against PH, and could be a relevant target for a new therapeutic strategy, using attractive H₂S-releasing molecules. Thus, the present review discusses the involvement and dysregulation of H₂S metabolism in pulmonary circulation pathophysiology.