{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T18:02:38Z","timestamp":1788804158471,"version":"build-2803163510"},"reference-count":49,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2018,10,3]],"date-time":"2018-10-03T00:00:00Z","timestamp":1538524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ivabradine, the selective inhibitor of the If current in the sinoatrial node, exerts cardiovascular protection by its bradycardic effect and potentially pleiotropic actions. However, there is a shortage of data regarding ivabradine\u2019s interaction with the renin-angiotensin-aldosterone system (RAAS). This study investigated whether ivabradine is able to protect a hypertensive heart in the model of L-NAME-induced hypertension and to interfere with the RAAS. Four groups (n = 10\/group) of adult male Wistar rats were treated as follows for four weeks: control, ivabradine (10 mg\/kg\/day), L-NAME (40 mg\/kg\/day), and L-NAME plus ivabradine. L-NAME administration increased systolic blood pressure (SBP) and left ventricular (LV) weight, enhanced hydroxyproline concentration in the LV, and deteriorated the systolic and diastolic LV function. Ivabradine reduced heart rate (HR) and SBP, and improved the LV function. The serum concentrations of angiotensin Ang 1\u20138 (Ang II), Ang 1\u20135, Ang 1\u20137, Ang 1\u201310, Ang 2\u20138, and Ang 3\u20138 were decreased in the L-NAME group and ivabradine did not modify them. The serum concentration of aldosterone and the aldosterone\/Ang II ratio were enhanced by L-NAME and ivabradine reduced these changes. We conclude that ivabradine improved the LV function of the hypertensive heart in L-NAME-induced hypertension. The protective effect of ivabradine might have been associated with the reduction of the aldosterone level.<\/jats:p>","DOI":"10.3390\/ijms19103017","type":"journal-article","created":{"date-parts":[[2018,10,4]],"date-time":"2018-10-04T02:19:49Z","timestamp":1538619589000},"page":"3017","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Effect of Ivabradine on a Hypertensive Heart and the Renin-Angiotensin-Aldosterone System in L-NAME-Induced Hypertension"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9922-4885","authenticated-orcid":false,"given":"Fedor","family":"Simko","sequence":"first","affiliation":[{"name":"Institute of Pathophysiology, Faculty of Medicine, Comenius University, Sasinkova 4, 81108 Bratislava, Slovakia"},{"name":"3rd Department of Internal Medicine, Faculty of Medicine, Comenius University, 83305 Bratislava, Slovakia"},{"name":"Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, 84505 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4752-9828","authenticated-orcid":false,"given":"Tomas","family":"Baka","sequence":"additional","affiliation":[{"name":"Institute of Pathophysiology, Faculty of Medicine, Comenius University, Sasinkova 4, 81108 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marko","family":"Poglitsch","sequence":"additional","affiliation":[{"name":"Attoquant Diagnostics, 1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7235-1710","authenticated-orcid":false,"given":"Kristina","family":"Repova","sequence":"additional","affiliation":[{"name":"Institute of Pathophysiology, Faculty of Medicine, Comenius University, Sasinkova 4, 81108 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Aziriova","sequence":"additional","affiliation":[{"name":"Institute of Pathophysiology, Faculty of Medicine, Comenius University, Sasinkova 4, 81108 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Krajcirovicova","sequence":"additional","affiliation":[{"name":"Institute of Pathophysiology, Faculty of Medicine, Comenius University, Sasinkova 4, 81108 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Zorad","sequence":"additional","affiliation":[{"name":"Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, 84505 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Adamcova","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Charles University, 50003 Hradec Kralove, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3834-7395","authenticated-orcid":false,"given":"Ludovit","family":"Paulis","sequence":"additional","affiliation":[{"name":"Institute of Pathophysiology, Faculty of Medicine, Comenius University, Sasinkova 4, 81108 Bratislava, Slovakia"},{"name":"Institute of Normal and Pathological Physiology, Center for Experimental Medicine, Slovak Academy of Sciences, 81371 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,10,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"305","DOI":"10.3389\/fphys.2016.00305","article-title":"Chronic Treatment with Ivabradine Does Not Affect Cardiovascular Autonomic Control in Rats","volume":"7","author":"Silva","year":"2016","journal-title":"Front. 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