{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T15:30:24Z","timestamp":1790523024629,"version":"4.1.0"},"reference-count":57,"publisher":"American Physiological Society","issue":"6","funder":[{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)","doi-asserted-by":"publisher","award":["HL82799"],"award-info":[{"award-number":["HL82799"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)","doi-asserted-by":"publisher","award":["HL007736"],"award-info":[{"award-number":["HL007736"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)","doi-asserted-by":"publisher","award":["HL123301"],"award-info":[{"award-number":["HL123301"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association (AHA)","doi-asserted-by":"publisher","award":["#12POST8690008"],"award-info":[{"award-number":["#12POST8690008"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association (AHA)","doi-asserted-by":"publisher","award":["#15GRNT21080001"],"award-info":[{"award-number":["#15GRNT21080001"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2016,12,1]]},"abstract":"<jats:p>\n                    Hydrogen sulfide (H\n                    <jats:sub>2<\/jats:sub>\n                    S) is a recently described gaseous vasodilator produced within the vasculature by the enzymes cystathionine \u03b3-lyase and 3-mercaptopyruvate sulfurtransferase. Previous data demonstrate that endothelial cells (EC) are the source of endogenous H\n                    <jats:sub>2<\/jats:sub>\n                    S production and are required for H\n                    <jats:sub>2<\/jats:sub>\n                    S-induced dilation. However, the signal transduction pathway activated by H\n                    <jats:sub>2<\/jats:sub>\n                    S within EC has not been elucidated. TRPV4 and large-conductance Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -activated K channels (BK channels) are expressed in EC. H\n                    <jats:sub>2<\/jats:sub>\n                    S-induced dilation is inhibited by luminal administration of iberiotoxin and disruption of the endothelium. Calcium influx through TRPV4 may activate these endothelial BK channels (eBK). We hypothesized that H\n                    <jats:sub>2<\/jats:sub>\n                    S-mediated vasodilation involves activation of TRPV4 within the endothelium. In pressurized, phenylephrine-constricted mesenteric arteries, H\n                    <jats:sub>2<\/jats:sub>\n                    S elicited a dose-dependent vasodilation blocked by inhibition of TRPV4 channels (GSK2193874A, 300 nM). H\n                    <jats:sub>2<\/jats:sub>\n                    S (1 \u03bcM) increased TRPV4-dependent (1.8-fold) localized calcium events in EC of pressurized arteries loaded with fluo-4 and Oregon Green. In pressurized EC tubes, H\n                    <jats:sub>2<\/jats:sub>\n                    S (1 \u03bcM) and the TRPV4 activator, GSK101679A (30 nM), increased calcium events 1.8- and 1.5-fold, respectively. H\n                    <jats:sub>2<\/jats:sub>\n                    S-induced an iberiotoxin-sensitive outward current measured using whole cell patch-clamp techniques in freshly dispersed EC. H\n                    <jats:sub>2<\/jats:sub>\n                    S increased K\n                    <jats:sup>+<\/jats:sup>\n                    currents from 10 to 30 pA\/pF at +150 mV. Treatment with Na\n                    <jats:sub>2<\/jats:sub>\n                    S increased the level of sulfhydration of TRPV4 channels in aortic ECs. These results demonstrate that H\n                    <jats:sub>2<\/jats:sub>\n                    S-mediated vasodilation involves activation of TRPV4-dependent Ca\n                    <jats:sup>2+<\/jats:sup>\n                    influx and BK channel activation within EC. Activation of TRPV4 channels appears to cause calcium events that result in the opening of eBK channels, endothelial hyperpolarization, and subsequent vasodilation.\n                  <\/jats:p>","DOI":"10.1152\/ajpheart.00465.2016","type":"journal-article","created":{"date-parts":[[2016,10,7]],"date-time":"2016-10-07T23:21:35Z","timestamp":1475882495000},"page":"H1437-H1444","source":"Crossref","is-referenced-by-count":89,"title":["Hydrogen sulfide-induced vasodilation mediated by endothelial TRPV4 channels"],"prefix":"10.1152","volume":"311","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5725-4664","authenticated-orcid":false,"given":"Jay S.","family":"Naik","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, New Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica M.","family":"Osmond","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, New Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjimen R.","family":"Walker","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, New Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy L.","family":"Kanagy","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, University of New Mexico, Albuquerque, New 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