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

Abstract

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.

Keywords: hydrogen sulfide; hydrogen sulfide-donors; oxidative stress; pyrogallol; superoxide anion; vascular endothelium; vasodilation.

Figure 1

Structures of H₂S donor molecules.

Figure 2

Vasodilating effects on rat aorta strips precontracted with 25 mM KCl: (a) 6 (dotted line, ●), 6 and 10 μM glibenclamide (straight line, ○); (b) 8 (dotted line, ■), 8 and 10 μM glibenclamide (straight line, □).

Figure 3

Effect of 6 (100 μM) on acetylcholine-induced vasodilation in endothelium-intact rat aortic rings. Control: rings incubated with vehicle only (DMSO) (straight line, □); rings incubated with 6 (straight line, ○); rings incubated with 500 μM pyrogallol (straight line, ■); rings incubated with 6 and 500 μM pyrogallol (straight line, ●); rings incubated with catechin (10 mM) and 500 μM pyrogallol (dotted line, ∆). Statistical analyses were made using Student’s t-test for unpaired data. ** p < 0.01 vs. the pyrogallol group.