Effect of Ivabradine on a Hypertensive Heart and the Renin-Angiotensin-Aldosterone System in L-NAME-Induced Hypertension
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’s interaction with the renin-angiotensin-aldosterone syste...
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doaj-1783a3c652a546b4966c90f5551403092020-11-25T00:16:49ZengMDPI AGInternational Journal of Molecular Sciences1422-00672018-10-011910301710.3390/ijms19103017ijms19103017Effect of Ivabradine on a Hypertensive Heart and the Renin-Angiotensin-Aldosterone System in L-NAME-Induced HypertensionFedor Simko0Tomas Baka1Marko Poglitsch2Kristina Repova3Silvia Aziriova4Kristina Krajcirovicova5Stefan Zorad6Michaela Adamcova7Ludovit Paulis8Institute of Pathophysiology, Faculty of Medicine, Comenius University, Sasinkova 4, 81108 Bratislava, SlovakiaInstitute of Pathophysiology, Faculty of Medicine, Comenius University, Sasinkova 4, 81108 Bratislava, SlovakiaAttoquant Diagnostics, 1030 Vienna, AustriaInstitute of Pathophysiology, Faculty of Medicine, Comenius University, Sasinkova 4, 81108 Bratislava, SlovakiaInstitute of Pathophysiology, Faculty of Medicine, Comenius University, Sasinkova 4, 81108 Bratislava, SlovakiaInstitute of Pathophysiology, Faculty of Medicine, Comenius University, Sasinkova 4, 81108 Bratislava, SlovakiaInstitute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, 84505 Bratislava, SlovakiaDepartment of Physiology, School of Medicine, Charles University, 50003 Hradec Kralove, Czech RepublicInstitute of Pathophysiology, Faculty of Medicine, Comenius University, Sasinkova 4, 81108 Bratislava, SlovakiaIvabradine, 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’s 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 1–8 (Ang II), Ang 1–5, Ang 1–7, Ang 1–10, Ang 2–8, and Ang 3–8 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.http://www.mdpi.com/1422-0067/19/10/3017ivabradineL-NAMEhypertensionfibrosisangiotensin IIaldosteroneheart function |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Fedor Simko Tomas Baka Marko Poglitsch Kristina Repova Silvia Aziriova Kristina Krajcirovicova Stefan Zorad Michaela Adamcova Ludovit Paulis |
spellingShingle |
Fedor Simko Tomas Baka Marko Poglitsch Kristina Repova Silvia Aziriova Kristina Krajcirovicova Stefan Zorad Michaela Adamcova Ludovit Paulis Effect of Ivabradine on a Hypertensive Heart and the Renin-Angiotensin-Aldosterone System in L-NAME-Induced Hypertension International Journal of Molecular Sciences ivabradine L-NAME hypertension fibrosis angiotensin II aldosterone heart function |
author_facet |
Fedor Simko Tomas Baka Marko Poglitsch Kristina Repova Silvia Aziriova Kristina Krajcirovicova Stefan Zorad Michaela Adamcova Ludovit Paulis |
author_sort |
Fedor Simko |
title |
Effect of Ivabradine on a Hypertensive Heart and the Renin-Angiotensin-Aldosterone System in L-NAME-Induced Hypertension |
title_short |
Effect of Ivabradine on a Hypertensive Heart and the Renin-Angiotensin-Aldosterone System in L-NAME-Induced Hypertension |
title_full |
Effect of Ivabradine on a Hypertensive Heart and the Renin-Angiotensin-Aldosterone System in L-NAME-Induced Hypertension |
title_fullStr |
Effect of Ivabradine on a Hypertensive Heart and the Renin-Angiotensin-Aldosterone System in L-NAME-Induced Hypertension |
title_full_unstemmed |
Effect of Ivabradine on a Hypertensive Heart and the Renin-Angiotensin-Aldosterone System in L-NAME-Induced Hypertension |
title_sort |
effect of ivabradine on a hypertensive heart and the renin-angiotensin-aldosterone system in l-name-induced hypertension |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2018-10-01 |
description |
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’s 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 1–8 (Ang II), Ang 1–5, Ang 1–7, Ang 1–10, Ang 2–8, and Ang 3–8 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. |
topic |
ivabradine L-NAME hypertension fibrosis angiotensin II aldosterone heart function |
url |
http://www.mdpi.com/1422-0067/19/10/3017 |
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