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This results in compromised handling of Ca<jats:sup>2+<\/jats:sup> ions that trigger heart contractile machinery. Here, we demonstrate that thiol-containing compounds such as N-acetylcysteine (NAC), glutathione ethyl ester (et-GSH), oxidized tetraethylglutathione (tet-GSSG), oxidized glutathione (GSSG) and S-nitrosoglutathione (GSNO) are capable of reducing negative effects of hypoxia on isolated rat cardiomyocytes. Preincubation of cardiomyocytes with 0.1\u2009mM GSNO, 0.5\u2009mM et-GSH, GSSG, tet-GSSG or with 10\u2009mM NAC allows cells 5-times longer tolerate the hypoxic conditions and elicit regular Ca<jats:sup>2+<\/jats:sup> transients in response to electric pacing. The shape of Ca<jats:sup>2+<\/jats:sup> transients generated in the presence of GSNO, et-GSH and NAC was similar to that observed in normoxic control cardiomyocytes. The leader compound, GSNO, accelerated by 34% the recovery of normal contractile function of isolated rat heart subjected to ischemia-reperfusion. GSNO increased glutathionylation of Na,K-ATPase alpha-2 subunit, the principal ion-transporter of cardiac myocyte sarcolemma, which prevents irreversible oxidation of Na,K-ATPase and regulates its function to support normal Ca<jats:sup>2+<\/jats:sup> ion handling in hypoxic cardiomyocytes. Altogether, GSNO appears effective cardioprotector in hypoxic conditions worth further studies toward its cardiovascular application.<\/jats:p>","DOI":"10.1038\/s41598-019-41266-2","type":"journal-article","created":{"date-parts":[[2019,3,19]],"date-time":"2019-03-19T21:35:28Z","timestamp":1553031328000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Glutathione-related substances maintain cardiomyocyte contractile function in hypoxic conditions"],"prefix":"10.1038","volume":"9","author":[{"given":"Yuri M.","family":"Poluektov","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina Yu.","family":"Petrushanko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nidas A.","family":"Undrovinas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina A.","family":"Lakunina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7889-3337","authenticated-orcid":false,"given":"Asker Y.","family":"Khapchaev","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valery I.","family":"Kapelko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander A.","family":"Abramov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir L.","family":"Lakomkin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikhail S.","family":"Novikov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir P.","family":"Shirinsky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1517-1983","authenticated-orcid":false,"given":"Vladimir A.","family":"Mitkevich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander A.","family":"Makarov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,3,19]]},"reference":[{"key":"41266_CR1","first-page":"3129","volume":"20","author":"T Vanek","year":"2014","unstructured":"Vanek, T. et al. 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