{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T01:29:24Z","timestamp":1767835764701,"version":"3.49.0"},"reference-count":61,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T00:00:00Z","timestamp":1725840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Changes in K<jats:sup>+<\/jats:sup> channel expression\/function are associated with disruption of vascular reactivity in several pathological conditions, including hypertension, diabetes, and atherosclerosis. Gasotransmitters achieve part of their effects in the organism by regulating ion channels, especially K<jats:sup>+<\/jats:sup> channels. Their involvement in hydrogen sulfide (H<jats:sub>2<\/jats:sub>S)\u2010mediated vasorelaxation is still unclear, and data about human vessels are limited.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine the role of K<jats:sup>+<\/jats:sup> channel subtypes in the vasorelaxant mechanism of H<jats:sub>2<\/jats:sub>S donor, sodium\u2010hydrosulfide (NaHS), on isolated human internal mammary artery (HIMA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>NaHS (1\u2009\u00d7\u200910<jats:sup>\u22126<\/jats:sup>\u20133\u2009\u00d7\u200910<jats:sup>\u22123<\/jats:sup>\u00a0mol\/L) induced a concentration\u2010dependent relaxation of HIMA pre\u2010contracted by phenylephrine and high K<jats:sup>+<\/jats:sup>. Among K<jats:sup>+<\/jats:sup> channel blockers, iberiotoxin, glibenclamide, 4\u2010aminopyridine (4\u2010AP), and margatoxin significantly inhibited NaHS\u2010induced relaxation of phenylephrine\u2010contracted HIMA (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01), whereas in the presence of apamin\/1\u2010[(2\u2010chlorophenyl) diphenylmethyl]\u20101H\u2010pyrazole (TRAM\u201034) combination, the HIMA relaxation was partially reduced (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). The effect of NaHS was antagonized by NO pathway inhibitors, L\u2010NAME and KT5823, and by cyclo\u2010oxygenase inhibitor, indomethacin (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01). Under conditions of blocked NO\/prostacyclin synthesis and release, apamin\/TRAM\u201034 and glibenclamide caused further decrease in NaHS\u2010induced vasorelaxation (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01), while iberiotoxin, 4\u2010AP, and margatoxin were without additional effect (<jats:italic>P<\/jats:italic>\u2009&gt;\u20090.05). In the presence of nifedipine, NaHS induced partial relaxation of HIMA (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results demonstrated that H<jats:sub>2<\/jats:sub>S donor, NaHS, induced concentration\u2010dependent relaxation of isolated HIMA. Vasorelaxant mechanisms of H<jats:sub>2<\/jats:sub>S included direct or indirect opening of different K<jats:sup>+<\/jats:sup> channel subtypes, K<jats:sub>ATP<\/jats:sub>, BK<jats:sub>Ca<\/jats:sub>, SK<jats:sub>Ca<\/jats:sub>\/IK<jats:sub>Ca<\/jats:sub>, and K<jats:sub>V<\/jats:sub> (subtype K<jats:sub>V<\/jats:sub>1.3), in addition to NO pathway activation and interference with extracellular Ca<jats:sup>2+<\/jats:sup> influx.<\/jats:p><\/jats:sec>","DOI":"10.1111\/fcp.13036","type":"journal-article","created":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T07:05:03Z","timestamp":1725865503000},"page":"1155-1167","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Involvement of different K<sup>+<\/sup> channel subtypes in hydrogen sulfide\u2010induced vasorelaxation of human internal mammary artery"],"prefix":"10.1111","volume":"38","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 Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan","family":"Stojanovic","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Belgrade  Belgrade Serbia"},{"name":"Institute for Cardiovascular Diseases \u201cDedinje\u201d  Belgrade Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Predrag","family":"Milojevic","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Belgrade  Belgrade Serbia"},{"name":"Institute for Cardiovascular Diseases \u201cDedinje\u201d  Belgrade 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