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The contractile effect occurs within a concentration range of 10\u00a0nM to 3\u00a0\u03bcM followed by vasodilatation at 30\u2013100\u2009\u03bcM. Here, we have investigated the signalling involved in the H<jats:sub>2<\/jats:sub>S\u2010induced contraction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Vascular response to NaHS or <jats:sc>l<\/jats:sc>\u2010cysteine is evaluated on isolated precontracted with phenylephrine vessel rings harvested from wild type, cystathionine \u03b3\u2010lyase (CSE<jats:sup>\u2212\/\u2212<\/jats:sup>), soluble guanylyl cyclase (sGC<jats:sub>\u03b11<\/jats:sub><jats:sup>\u2212\/\u2212<\/jats:sup>) and endothelial nitric oxide synthase (eNOS<jats:sup>\u2212\/\u2212<\/jats:sup>) knock\u2010out mice. The cAMP, cGMP and inosine 3\u2032,5\u2032\u2010cyclic monophosphate (cIMP) levels are simultaneously quantified using ultra\u2010performance liquid chromatography\u2013tandem mass spectrometry (UPLC\u2010MS\/MS) analysis. The involvement of sGC, phosphodiesterase (PDE) 4A and PDE5 are also evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>CSE\u2010derived H<jats:sub>2<\/jats:sub>S\u2010induced contraction requires an intact eNOS\/NO\/sGC pathway and involves cIMP as a second messenger. H<jats:sub>2<\/jats:sub>S contractile effect involves a transient increase of cGMP and cAMP metabolism caused by PDE5 and PDE4A, thus unmasking cIMP contracting action. The stable cell\u2010permeable analogue of cIMP elicits concentration\u2010dependent contraction on a stable background tone induced by phenylephrine. The lack of cIMP, coupled to the hypocontractility displayed by vessels harvested from CSE<jats:sup>\u2212\/\u2212<\/jats:sup> mice, confirms that H<jats:sub>2<\/jats:sub>S\u2010induced contraction involves cIMP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>The endothelium dynamically regulates vessel homeostasis by modulating contractile tone. This also involves CSE\u2010derived H<jats:sub>2<\/jats:sub>S that is mediated by cIMP.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15516","type":"journal-article","created":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T05:54:26Z","timestamp":1619848466000},"page":"3765-3782","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Involvement of 3\u2032,5\u2032\u2010cyclic inosine monophosphate in cystathionine \u03b3\u2010lyase\u2010dependent regulation of the vascular tone"],"prefix":"10.1111","volume":"178","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4372-9611","authenticated-orcid":false,"given":"Emma","family":"Mitidieri","sequence":"first","affiliation":[{"name":"Department of Pharmacy, School of Medicine and Surgery University of Naples Federico II  Naples 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