Hydrogen Sulphide: Biopharmacological Roles in the Cardiovascular System and Pharmaceutical Perspectives

Hydrogen sulphide (H2S) is now viewed as an important endogenous gasotransmitter, which exhibits many beneficial effects on the cardiovascular system. H2S is biosynthesized in mammalian tissues by both non-enzymatic processes and several enzymatic pathways ensured by cystathionine-beta-synthase and cystathionine-gamma-lyase. H2S is endowed with the antioxidant properties of inorganic and organic sulphites, being a scavenger of reactive oxygen species. Furthermore, H2S triggers other important effects and the activation of ATP-sensitive potassium channels (K-ATP) accounts for its vasorelaxing and cardioprotective effects. H2S also inhibits smooth muscle proliferation and platelet aggregation. Conversely, the impairment of H2S contributes to the pathogenesis of hypertension and is involved in cardiovascular complications associated with diabetes mellitus. There is also evidence of a link between H2S and endothelial nitric oxide (NO). Recent observations indicate a possible pathogenic link between deficiencies of H2S activity and the progress of endothelial dysfunction. These biological aspects of endogenous H2S led to consider this mediator as the new NO and to evaluate new attractive opportunities to develop innovative classes of drugs. In this review, the main roles played by H2S in the cardiovascular system and the first examples of H2S-donor drugs are discussed. Some hybrid drugs are also addressed in this review. In such compounds opportune H2S-releasing moieties are conjugated to well-known drugs to improve their pharmacodynamic profile or to reduce the potential for adverse effects.