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Herein, it is demonstrated that administration of H<jats:sub>2<\/jats:sub>S as intravenous sodium sulfide (Na<jats:sub>2<\/jats:sub>S) increased blood pressure in sheep and rats, and this effect persisted after H<jats:sub>2<\/jats:sub>S has disappeared from the blood. Inhibition of the L\u2010type calcium channel (LTCC) diminished the hypertensive effects. Incubation of Na<jats:sub>2<\/jats:sub>S with whole blood, red blood cells, methemoglobin, or oxyhemoglobin produced a hypertensive product of H<jats:sub>2<\/jats:sub>S, which is not hydrogen thioperoxide, metHb\u2010SH<jats:sup>\u2212<\/jats:sup> complexes, per\u2010\/poly\u2010 sulfides, or thiolsulfate, but rather a labile intermediate. One\u2010electron oxidation of H<jats:sub>2<\/jats:sub>S by oxyhemoglobin generated its redox cousin, sulfhydryl radical (HS<jats:bold><jats:sup>\u2022<\/jats:sup>)<\/jats:bold>. Consistent with the role of HS<jats:bold><jats:sup>\u2022<\/jats:sup><\/jats:bold> as the hypertensive intermediate, scavenging HS<jats:bold><jats:sup>\u2022<\/jats:sup><\/jats:bold> inhibited Na<jats:sub>2<\/jats:sub>S\u2010induced vasoconstriction and activation of LTCCs. In conclusion, H<jats:sub>2<\/jats:sub>S causes vasoconstriction that is dependent on the activation of LTCCs and generation of HS<jats:bold><jats:sup>\u2022<\/jats:sup><\/jats:bold> by oxyhemoglobin.<\/jats:p>","DOI":"10.1002\/advs.202305866","type":"journal-article","created":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T00:45:13Z","timestamp":1714437913000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["H<sub>2<\/sub>S\u00a0Increases Blood Pressure via Activation of L\u2010Type Calcium Channels with Mediation by HS<sup>\u2022<\/sup>\u00a0Generated from Reactions with Oxyhemoglobin"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1451-7951","authenticated-orcid":false,"given":"Taiming","family":"Liu","sequence":"first","affiliation":[{"name":"Division of Neonatology Department of Pediatrics Loma Linda University School of Medicine  Loma Linda CA 92354 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meijuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Neonatology Department of Pediatrics Loma Linda University School of Medicine  Loma Linda CA 92354 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn","family":"Hanson","sequence":"additional","affiliation":[{"name":"Lawrence D. 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