{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T20:28:58Z","timestamp":1787171338786,"version":"build-2736575974"},"posted":{"date-parts":[[2026,8,16]]},"group-title":"Physiology","reference-count":64,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T00:00:00Z","timestamp":1786838400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["HL160606-04"],"award-info":[{"award-number":["HL160606-04"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["NCI 2P30 CA118100"],"award-info":[{"award-number":["NCI 2P30 CA118100"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>\n                    Hydrogen sulfide (H\n                    <jats:sub>2<\/jats:sub>\n                    S) is an important endothelial-derived vasodilator, but the signaling mechanism remains incompletely understood. We previously demonstrated that H\n                    <jats:sub>2<\/jats:sub>\n                    S-mediated vasodilation requires transient receptor potential vanilloid type 4 (TRPV4) channels. Because H\n                    <jats:sub>2<\/jats:sub>\n                    S has been reported to enhance heme oxygenase (HO) activity and HO-derived carbon monoxide (CO) regulates endothelial signaling, we hypothesized that H\n                    <jats:sub>2<\/jats:sub>\n                    S-mediated vasodilation requires HO-2-derived CO.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    Pressure myography was performed in isolated rat mesenteric arteries to determine the contribution of HO, TRPV4, eBK, and SK\/IK channels to H\n                    <jats:sub>2<\/jats:sub>\n                    S-mediated vasodilation. HO-2 sulfhydration was assessed using a maleimide assay, and spatial association among HO-2 and TRPV4 was examined using proximity ligation assays in human aortic endothelial cells.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    H\n                    <jats:sub>2<\/jats:sub>\n                    S Selicited concentration-dependent vasodilation that was abolished by HO inhibition. Repletion of CO restored H\n                    <jats:sub>2<\/jats:sub>\n                    S-mediated vasodilation in the presence of HO inhibition. CO-mediated vasodilation was abolished by TRPV4 and SK\/IK inhibition but was unaffected by eBK inhibition. H\n                    <jats:sub>2<\/jats:sub>\n                    S increased HO-2 sulfhydration and enhanced HO activity. In endothelial cells, HO-2 and TRPV4 exhibited close spatial association.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>\n                    These findings support a model in which H\n                    <jats:sub>2<\/jats:sub>\n                    S stimulates HO-2-derived CO production, leading to TRPV4-dependent endothelial signaling, SK\/IK activation, and vasodilation. Together, the data support the existence of an endothelial HO-2\/TRPV4\/SK\/IK signaling domain that contributes to H\n                    <jats:sub>2<\/jats:sub>\n                    S-mediated vascular reactivity.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.08.11.744278","type":"posted-content","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T04:40:26Z","timestamp":1786941626000},"source":"Crossref","is-referenced-by-count":0,"title":["Hydrogen sulfide-mediated vasodilation requires heme oxygenase-derived carbon monoxide"],"prefix":"10.64898","author":[{"given":"Jacob R","family":"Anderson","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Physiology, University of New Mexico Health Science Center, Albuquerque, New Mexico, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crystal X","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, University of New Mexico Health Science Center, Albuquerque, New Mexico, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura V","family":"Gonzalez Bosc","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, University of New Mexico Health Science Center, Albuquerque, New Mexico, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay S","family":"Naik","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, University of New Mexico Health Science Center, Albuquerque, New Mexico, 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