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Arginase is involved in development of myocardial <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content> injury driven by inflammatory mediators. The aim of the study was to clarify whether <jats:styled-content style=\"fixed-case\">VNS<\/jats:styled-content> downregulates myocardial and vascular arginase via a mechanism involving activation of \u03b17 n<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>hR following myocardial IR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Anaesthetized rats were randomized to (i) sham\u2010operated, (ii) control <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content> (30\u2010min ischaemia and 2\u2010h reperfusion, (iii) <jats:styled-content style=\"fixed-case\">VNS<\/jats:styled-content> throughout <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>, (iv) the arginase inhibitor nor\u2010<jats:styled-content style=\"fixed-case\">NOHA<\/jats:styled-content>+<jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>, (v) nor\u2010<jats:styled-content style=\"fixed-case\">NOHA<\/jats:styled-content>+<jats:styled-content style=\"fixed-case\">VNS<\/jats:styled-content>+<jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>, (vi) selective \u03b17 n<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>hR blockade by methyllycaconitine (<jats:styled-content style=\"fixed-case\">MLA<\/jats:styled-content>) followed by <jats:styled-content style=\"fixed-case\">VNS<\/jats:styled-content> throughout <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content> and (vii) <jats:styled-content style=\"fixed-case\">MLA<\/jats:styled-content>+IR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Infarct size was reduced by <jats:styled-content style=\"fixed-case\">VNS<\/jats:styled-content> compared to control <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content> (41 \u00b1 3% vs. 67 \u00b1 2% of the myocardium at risk, <jats:italic>P<\/jats:italic> &lt; 0.001). Myocardial <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content> increased myocardial and aortic arginase activity 1.7\u2010 and 3.1\u2010fold respectively (<jats:italic>P<\/jats:italic> &lt; 0.05). <jats:styled-content style=\"fixed-case\">VNS<\/jats:styled-content> attenuated the increase in arginase activity compared to control <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content> both in the myocardium and aorta (<jats:italic>P<\/jats:italic> &lt; 0.05). <jats:styled-content style=\"fixed-case\">MLA<\/jats:styled-content> partially abolished the cardioprotective effect of <jats:styled-content style=\"fixed-case\">VNS<\/jats:styled-content> and completely abrogated the effect of <jats:styled-content style=\"fixed-case\">VNS<\/jats:styled-content> on arginase activity. Arginase inhibition combined with <jats:styled-content style=\"fixed-case\">VNS<\/jats:styled-content> did not further reduce infarct size.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Vagal nerve stimulation reduced infarct size and reversed the upregulation of arginase induced by <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content> both in the myocardium and aorta via a mechanism depending on \u03b17 n<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content>hR activation. The data suggest that the cardioprotective effect of <jats:styled-content style=\"fixed-case\">VNS<\/jats:styled-content> is mediated via reduction in arginase activity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.12861","type":"journal-article","created":{"date-parts":[[2017,2,27]],"date-time":"2017-02-27T01:06:40Z","timestamp":1488157600000},"page":"174-181","source":"Crossref","is-referenced-by-count":45,"title":["Vagal nerve stimulation reduces infarct size via a mechanism involving the alpha\u20107 nicotinic acetylcholine receptor and downregulation of cardiac and vascular arginase"],"prefix":"10.1111","volume":"221","author":[{"given":"A.","family":"Kiss","sequence":"first","affiliation":[{"name":"Department of Medicine Unit of Cardiology Karolinska Institutet Heart and Vascular Theme Karolinska University Hospital Stockholm Sweden"},{"name":"Ludwig Boltzmann Cluster for Cardiovascular Research at the Center for Biomedical Research Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Tratsiakovich","sequence":"additional","affiliation":[{"name":"Department of Medicine Unit of Cardiology Karolinska Institutet Heart and Vascular Theme Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Mahdi","sequence":"additional","affiliation":[{"name":"Department of Medicine Unit of Cardiology Karolinska Institutet Heart and Vascular Theme Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medicine Unit of Cardiology Karolinska Institutet Heart and Vascular Theme Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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