Comparative Study of Different H[sub.2]S Donors as Vasodilators and Attenuators of Superoxide-Induced Endothelial Damage

In the last years, research proofs have confirmed that hydrogen sulfide (H[sub.2] S) plays an important role in various physio-pathological processes, such as oxidation, inflammation, neurophysiology, and cardiovascular protection; in particular, the protective effects of H[sub.2] S in cardiovascular diseases were demonstrated. The interest in H[sub.2] S-donating molecules as tools for biological and pharmacological studies has grown, together with the understanding of H[sub.2] S importance. Here we performed a comparative study of a series of H[sub.2] S donor molecules with different chemical scaffolds and H[sub.2] S release mechanisms. The compounds were tested in human serum for their stability and ability to generate H[sub.2] S. 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. H[sub.2] S donors showed different H[sub.2] S-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 H[sub.2] S-releasing agents also conjugated with other pharmacophores.