Abstract
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 (H(2)S) has been described as the third gasotransmitter with plethoric regulatory functions in cardiovascular tissues, especially in pulmonary circulation. Alteration in H(2)S biogenesis has been associated with the hallmarks of PH. H(2)S 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, H(2)S modulates ATP-sensitive K(+) channel (K(ATP)) activity, and is associated with PA relaxation. In vitro or in vivo H(2)S supplementation exerts antioxidative and anti-inflammatory properties, and reduces PA remodeling. Altogether, current findings suggest that H(2)S promotes protective effects against PH, and could be a relevant target for a new therapeutic strategy, using attractive H(2)S-releasing molecules. Thus, the present review discusses the involvement and dysregulation of H(2)S metabolism in pulmonary circulation pathophysiology.