Comparative Study of Different H(2)S Donors as Vasodilators and Attenuators of Superoxide-Induced Endothelial Damage

不同H₂S供体作为血管扩张剂和超氧化物诱导内皮损伤抑制剂的比较研究

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Abstract

In the last years, research proofs have confirmed that hydrogen sulfide (H(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(2)S in cardiovascular diseases were demonstrated. The interest in H(2)S-donating molecules as tools for biological and pharmacological studies has grown, together with the understanding of H(2)S importance. Here we performed a comparative study of a series of H(2)S donor molecules with different chemical scaffolds and H(2)S release mechanisms. The compounds were tested in human serum for their stability and ability to generate H(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(2)S donors showed different H(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(2)S-releasing agents also conjugated with other pharmacophores.

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