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To address these contradictory findings, we analyzed cardiac functions in \u03b17 NR knockout mice (\u03b17<jats:sup>\u2212\/\u2212<\/jats:sup>) in vivo and ex vivo in isolated hearts. A standard limb leads electrocardiogram was used, and the pressure curves were recorded in vivo, in <jats:italic>Arteria carotis<\/jats:italic> and in the left ventricle, or ex vivo, in the left ventricle of the spontaneously beating isolated hearts perfused following Langedorff's method. Experiments were performed under basic conditions, hypercholinergic conditions, and adrenergic stress. The relative expression levels of \u03b1 and \u03b2 NR subunits, muscarinic receptors, \u03b21 adrenergic receptors, and acetylcholine life cycle markers were determined using RT\u2010qPCR. Our results revealed a prolonged QT interval in \u03b17<jats:sup>\u2212\/\u2212<\/jats:sup> mice. All in vivo hemodynamic parameters were preserved under all studied conditions. The only difference in ex vivo heart rate between genotypes was the loss of bradycardia in prolonged incubation of isoproterenol\u2010pretreated hearts with high doses of acetylcholine. In contrast, left ventricular systolic pressure was lower under basal conditions and showed a significantly higher increase during adrenergic stimulation. No changes in mRNA expression were observed. In conclusion, \u03b17 NR has no major effect on heart rate, except when stressed hearts are exposed to a prolonged hypercholinergic state, suggesting a role in acetylcholine spillover control. In the absence of extracardiac regulatory mechanisms, left ventricular systolic impairment is revealed.<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15821-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p>","DOI":"10.1111\/jnc.15821","type":"journal-article","created":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T14:39:55Z","timestamp":1680705595000},"page":"414-427","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["\u03b17 nicotinic receptors play a role in regulation of cardiac hemodynamics"],"prefix":"10.1111","volume":"168","author":[{"given":"Katarina","family":"Targosova","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, Department of Pharmacology and Toxicology Comenius University Bratislava  Bratislava Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matej","family":"Kucera","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Department of Pharmacology and Toxicology Comenius University Bratislava  Bratislava Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomas","family":"Fazekas","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy Department of Physical Chemistry of Drugs Comenius University Bratislava  Bratislava Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zuzana","family":"Kilianova","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Department of Pharmacology and Toxicology Comenius University Bratislava  Bratislava Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana","family":"Stankovicova","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Department of Pharmacology and Toxicology Comenius University Bratislava  Bratislava Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1713-872X","authenticated-orcid":false,"given":"Anna","family":"Hrabovska","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Department of Pharmacology and Toxicology Comenius University Bratislava  Bratislava Slovakia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,4,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-012-1075-1"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12917-014-0198-3"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00015.2008"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000080932.98903.D8"},{"issue":"192","key":"e_1_2_10_6_1","first-page":"197.e1","article-title":"Prolonged QTc intervals and decreased left ventricular contractility in patients with propionic acidemia","volume":"150","author":"Baumgartner D.","year":"2007","journal-title":"The Journal of Pediatrics"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehn219"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.87.4.275"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-13-05076.2000"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0163-7258(93)90030-H"},{"key":"e_1_2_10_11_1","first-page":"651","article-title":"Adrenergic and muscarinic receptors in the human heart","volume":"51","author":"Brodde O. 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