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As the mechanism of H<jats:sub>2<\/jats:sub>S\u2010induced relaxation in human vessels remains unclear, the present study aimed to investigate the effects of H<jats:sub>2<\/jats:sub>S donor, sodium hydrosulfide (NaHS), on isolated human saphenous vein (HSV) and to determine the mechanism of action. Our results showed that NaHS (1\u00a0\u00b5M\u20133\u00a0mM) induced a concentration\u2010dependent relaxation of endothelium\u2010intact HSV rings pre\u2010contracted by phenylephrine. Pre\u2010treatment with L\u2010NAME, ODQ and KT5823 significantly inhibited NaHS\u2010induced relaxation, while indomethacin induced partial inhibition. Among K<jats:sup>+<\/jats:sup> channel blockers, the combination of apamin and TRAM\u201034 significantly affected the relaxation produced by NaHS, while iberiotoxin and glibenclamide only reduced maximal relaxation of HSV. NaHS partially relaxed endothelium\u2010intact rings pre\u2010contracted by high K<jats:sup>+<\/jats:sup>, as well as phenylephrine\u2010contracted rings in the presence of nifedipine. Additionally, the incubation of HSV rings with NaHS increased NO production. These results demonstrate that NaHS produces the concentration\u2010 and endothelium\u2010dependent relaxation of isolated HSV. Vasorelaxation to NaHS probably involves activation of NO\/cGMP\/PKG pathway and partially prostacyclin. In addition, different K<jats:sup>+<\/jats:sup> channels subtypes, especially SK<jats:sub>Ca<\/jats:sub> and IK<jats:sub>Ca<\/jats:sub>, as well as BK<jats:sub>Ca<\/jats:sub> and K<jats:sub>ATP<\/jats:sub> channels in high concentrations of NaHS, probably participate in the NaHS\u2010induced vasorelaxation.<\/jats:p>","DOI":"10.1111\/fcp.12658","type":"journal-article","created":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T23:36:01Z","timestamp":1612308961000},"page":"906-918","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Mechanisms underlying the vasorelaxant effect of hydrogen sulfide on human saphenous vein"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9150-7381","authenticated-orcid":false,"given":"Marija","family":"Marinko","sequence":"first","affiliation":[{"name":"Department of Pharmacology Faculty of Pharmacy University of Belgrade  Belgrade 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