Comparative Study of Different H₂S Donors as Vasodilators and Attenuators of Superoxide-Induced Endothelial Damage

In the last years, research proofs have confirmed that hydrogen sulfide (H₂S) plays an important role in various physio-pathological processes, such as oxidation, inflammation, neurophysiology, and cardiovascular protection; in particular, the protective effects of H₂S in cardiovascular diseases were demonstrated. The interest in H₂S-donating molecules as tools for biological and pharmacological studies has grown, together with the understanding of H₂S importance. Here we performed a comparative study of a series of H₂S donor molecules with different chemical scaffolds and H₂S release mechanisms. The compounds were tested in human serum for their stability and ability to generate H₂S. Their vasorelaxant properties were studied on rat aorta strips, and the capacity of the selected compounds to protect NO-dependent endothelium reactivity in an acute oxidative stress model was tested. H₂S donors showed different H₂S-releasing kinetic and produced amounts and vasodilating profiles; in particular, compound 6 was able to attenuate the dysfunction of relaxation induced by pyrogallol exposure, showing endothelial protective effects. These results may represent a useful basis for the rational development of promising H₂S-releasing agents also conjugated with other pharmacophores.