{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T09:47:29Z","timestamp":1770457649060,"version":"3.49.0"},"reference-count":59,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T00:00:00Z","timestamp":1644364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2019\/14051-2"],"award-info":[{"award-number":["2019\/14051-2"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"publisher","award":["306294\/2019-2"],"award-info":[{"award-number":["306294\/2019-2"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfeicoamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["finance code 001"],"award-info":[{"award-number":["finance code 001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Mitochondria-targeted hydrogen sulfide (H2S) donor compounds, such as compound AP39, supply H2S into the mitochondrial environment and have shown several beneficial in vitro and in vivo effects in cardiovascular conditions such as diabetes and hypertension. However, the study of their direct vascular effects has not been addressed to date. Thus, the objective of the present study was to analyze the effects and describe the mechanisms of action of AP39 on the in vitro vascular reactivity of mouse mesenteric artery. Protein and gene expressions of the H2S-producing enzymes (CBS, CSE, and 3MPST) were respectively analyzed by Western blot and qualitative RT-PCR, as well the in vitro production of H2S by mesenteric artery homogenates. Gene expression of CSE and 3MPST in the vessels has been evidenced by RT-PCR experiments, whereas the protein expression of all the three enzymes was demonstrated by Western blotting experiments. Nonselective inhibition of H2S-producing enzymes by AOAA abolished H2S production, whereas it was partially inhibited by PAG (a CSE selective inhibitor). Vasorelaxation promoted by AP39 and its H2S-releasing moiety (ADT-OH) were significantly reduced after endothelium removal, specifically dependent on NO-cGMP signaling and SKCa channel opening. Endogenous H2S seems to participate in the mechanism of action of AP39, and glibenclamide-induced KATP blockade did not affect the vasorelaxant response. Considering the results of the present study and the previously demonstrated antioxidant and bioenergetic effects of AP39, we conclude that mitochondria-targeted H2S donors may offer a new promising perspective in cardiovascular disease therapeutics.<\/jats:p>","DOI":"10.3390\/biom12020280","type":"journal-article","created":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T21:19:06Z","timestamp":1644441546000},"page":"280","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Vasorelaxant Activity of AP39, a Mitochondria-Targeted H2S Donor, on Mouse Mesenteric Artery Rings In Vitro"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6022-1460","authenticated-orcid":false,"given":"Leonardo A. da Costa","family":"da Costa Marques","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-000, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone A.","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-000, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fl\u00e1via N. de","family":"de Jesus","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-000, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark E.","family":"Wood","sequence":"additional","affiliation":[{"name":"Medical School, University of Exeter, Exeter EX1 2LU, UK"},{"name":"School of Biosciences, University of Exeter, Exeter EX4 4QD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberta","family":"Torregrossa","sequence":"additional","affiliation":[{"name":"Medical School, University of Exeter, Exeter EX1 2LU, UK"},{"name":"School of Biosciences, University of Exeter, Exeter EX4 4QD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Whiteman","sequence":"additional","affiliation":[{"name":"Medical School, University of Exeter, Exeter EX1 2LU, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2574-4490","authenticated-orcid":false,"given":"Soraia K. P.","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-000, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcelo N.","family":"Muscar\u00e1","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo 05508-000, SP, Brazil"},{"name":"Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 4N1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1523\/JNEUROSCI.16-03-01066.1996","article-title":"The possible role of hydrogen sulfide as an endogenous neuromodulator","volume":"16","author":"Abe","year":"1996","journal-title":"J. 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