Regulation of blood pressure by natural sulfur compounds: Focus on their mechanisms of action.

Natural sulfur compounds are emerging as therapeutic options for the management of hypertension and prehypertension. They are mainly represented by polysulfides from Alliaceae (i.e., garlic) and isothiocyanates from Brassicaceae (or crucifers). The beneficial cardiovascular effects of these compounds, especially garlic polysulfides, are well known and widely reported both in preclinical and clinical studies. However, only a few authors have linked the ability of natural sulfur compounds to induce vasorelaxation and subsequent antihypertensive effects with their ability to release hydrogen sulfide (HS) in biological tissue. HS is an endogenous gasotransmitter involved in vascular tone regulation. Some cardiovascular diseases, such as hypertension, are associated with lower plasma HS levels. Consequently, exogenous sources of HS (HS donors) have been designed and synthesized or identified among secondary plant metabolites as potential therapeutic options. In addition to antioxidant effects due to its chemical properties as a reducing agent, HS induces vasorelaxation by interacting with a range of molecular targets. The mechanisms of action accounting for HS-induced vasodilation include opening of vascular potassium channels (such as ATP-sensitive (K) and voltage-operated (Kv7) channels), inhibition of 5-phosphodiesterase (5-PDE), and activation of vascular endothelial growth factor receptor-2 (VEGFR-2). These effects may be attributed to HS-induced S-persulfidation (or S-sulfhydration), which is a posttranslational modification of cysteine residues of many types of proteins resulting in structural and functional alterations (activation/inhibition). Thus, HS donors, such as natural sulfur compounds, are promising antihypertensive agents with novel mechanisms of action.