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We have previously demonstrated that <jats:styled-content style=\"fixed-case\">GH<\/jats:styled-content> secretagogues and the ghrelin gene\u2010derived peptides, including obestatin, exert cardiovascular effects by modulating cardiac inotropism and vascular tone, and reducing cell death and contractile dysfunction in hearts subjected to ischaemia\/reperfusion (I\/R), through the Akt\/nitric oxide (<jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content>) pathway. However, the mechanisms underlying the cardiac actions of obestatin remain largely unknown. Thus, we suggested that obestatin\u2010induced activation of <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K\/Akt\/<jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">PKG<\/jats:styled-content> signalling is implicated in protection of the myocardium when challenged by adrenergic, endothelinergic or I\/R stress. We show that obestatin exerts an inhibitory tone on the performance of rat papillary muscle in both basal conditions and under \u03b2\u2010adrenergic overstimulation, through endothelial\u2010dependent <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">cGMP<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PKG<\/jats:styled-content> signalling. This pathway was also involved in the vasodilator effect of the peptide, used both alone and under stress induced by endothelin\u20101. Moreover, when infused during early reperfusion, obestatin reduced infarct size in isolated I\/R rat hearts, through an <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PKG<\/jats:styled-content> pathway, comprising <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PKC<\/jats:styled-content> signalling, and converging on mitochondrial <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>\u2010sensitive potassium [mitoK(<jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>)] channels. Overall, our results suggest that obestatin regulates cardiovascular function in stress conditions and induces cardioprotection by mechanisms dependent on activation of an <jats:styled-content style=\"fixed-case\">NO<\/jats:styled-content>\/soluble guanylate cyclase (<jats:styled-content style=\"fixed-case\">sGC<\/jats:styled-content>)\/<jats:styled-content style=\"fixed-case\">PKG<\/jats:styled-content> pathway. In fact, obestatin counteracts exaggerated \u03b2\u2010adrenergic and endothelin\u20101 activity, relevant factors in heart failure, suggesting multiple positive effects of the peptide, including the lowering of cardiac afterload, thus representing a potential candidate in pharmacological post\u2010conditioning.<\/jats:p>","DOI":"10.1111\/jcmm.13277","type":"journal-article","created":{"date-parts":[[2017,7,26]],"date-time":"2017-07-26T07:28:39Z","timestamp":1501054119000},"page":"3670-3678","source":"Crossref","is-referenced-by-count":29,"title":["Obestatin regulates cardiovascular function and promotes cardioprotection through the nitric oxide pathway"],"prefix":"10.1111","volume":"21","author":[{"given":"Claudia","family":"Penna","sequence":"first","affiliation":[{"name":"Department of Clinical and Biological Sciences University of Turin Turin Italy"},{"name":"National Institute of Cardiovascular Research Bologna Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Tullio","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences University of Turin Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saveria","family":"Femmin\u00f2","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences University of Turin Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmine","family":"Rocca","sequence":"additional","affiliation":[{"name":"National Institute of Cardiovascular Research Bologna Italy"},{"name":"Department of Biology, Ecology and E.S. 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