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Concomitant administration of simvastatin with ivabradine in contrast to metoprolol intensifies slowing of heart rate in normo- and hypercholesterolemic rats

INTRODUCTION: β-Blockers play a significant role in therapeutic heart rate (HR) management and angina control. In patients who are unable to tolerate β-blockers ivabradine could be particularly useful. The aim of the study was to establish whether concomitant administration of simvastatin with ivabr...

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Autores principales: Owczarek, Jacek, Jasińska, Magdalena, Drożdż, Jarosław, Orszulak-Michalak, Daria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Termedia Publishing House 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400921/
https://www.ncbi.nlm.nih.gov/pubmed/22852014
http://dx.doi.org/10.5114/aoms.2012.29411
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author Owczarek, Jacek
Jasińska, Magdalena
Drożdż, Jarosław
Orszulak-Michalak, Daria
author_facet Owczarek, Jacek
Jasińska, Magdalena
Drożdż, Jarosław
Orszulak-Michalak, Daria
author_sort Owczarek, Jacek
collection PubMed
description INTRODUCTION: β-Blockers play a significant role in therapeutic heart rate (HR) management and angina control. In patients who are unable to tolerate β-blockers ivabradine could be particularly useful. The aim of the study was to establish whether concomitant administration of simvastatin with ivabradine or metoprolol had any effect on rat HR and blood pressure (BP). MATERIAL AND METHODS: The experiments were performed in hyper- and normocholesterolemic outbred Wistar rats. Animals were divided into 2 groups: receiving during 4 weeks normal diet (normocholesterolemic rats) or diet with 5% cholesterol and 2.5% cholic acid (hypercholesterolemic rats). Then rats received placebo (0.1% methylcellulose), 2) metoprolol 30 mg/kg bw; 3) ivabradine 10 mg/kg bw; 4) simvastatin 10 mg/kg bw; 5) simvastatin 10 mg/kg bw + metoprolol 30 mg/kg bw; 6) simvastatin 10 mg/kg bw + ivabradine 10 mg/kg bw. Drugs were given during a 4-week period. HR and BP measure were provided by an Isotec pressure transducer connected to a direct current bridge amplifier. For the further lipid profile examination, 0.25 ml of blood samples were taken. RESULTS: After administration of ivabradine with simvastatin to normocholesterolemic and hypercholesterolemic rats the mean HR was significantly reduced as compared to rats receiving simvastatin (312.0 ±30.2 min(−1) vs. 430.7 ±27.8 min(−1), p<0.05); (329.8 ±24.2 min(−1) vs. 420.5 ±9.2 min(−1), p<0.05) or ivabradine alone (312.0 ±30.2 min(−1) vs. 350.2 ±16.0 min(−1), p<0.05); (329.8 ±24.2 min(−1) vs. 363.0 ±21.7 min(−1), p<0.05). CONCLUSIONS: Concomitant administration of simvastatin with ivabradine intensified slowing of HR, although it did not influence BP in normo-and hypercholesterolemic rats. Statin-induced intensification of HR deceleration after metoprolol administration was not observed.
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spelling pubmed-34009212012-07-31 Concomitant administration of simvastatin with ivabradine in contrast to metoprolol intensifies slowing of heart rate in normo- and hypercholesterolemic rats Owczarek, Jacek Jasińska, Magdalena Drożdż, Jarosław Orszulak-Michalak, Daria Arch Med Sci Experimental Research INTRODUCTION: β-Blockers play a significant role in therapeutic heart rate (HR) management and angina control. In patients who are unable to tolerate β-blockers ivabradine could be particularly useful. The aim of the study was to establish whether concomitant administration of simvastatin with ivabradine or metoprolol had any effect on rat HR and blood pressure (BP). MATERIAL AND METHODS: The experiments were performed in hyper- and normocholesterolemic outbred Wistar rats. Animals were divided into 2 groups: receiving during 4 weeks normal diet (normocholesterolemic rats) or diet with 5% cholesterol and 2.5% cholic acid (hypercholesterolemic rats). Then rats received placebo (0.1% methylcellulose), 2) metoprolol 30 mg/kg bw; 3) ivabradine 10 mg/kg bw; 4) simvastatin 10 mg/kg bw; 5) simvastatin 10 mg/kg bw + metoprolol 30 mg/kg bw; 6) simvastatin 10 mg/kg bw + ivabradine 10 mg/kg bw. Drugs were given during a 4-week period. HR and BP measure were provided by an Isotec pressure transducer connected to a direct current bridge amplifier. For the further lipid profile examination, 0.25 ml of blood samples were taken. RESULTS: After administration of ivabradine with simvastatin to normocholesterolemic and hypercholesterolemic rats the mean HR was significantly reduced as compared to rats receiving simvastatin (312.0 ±30.2 min(−1) vs. 430.7 ±27.8 min(−1), p<0.05); (329.8 ±24.2 min(−1) vs. 420.5 ±9.2 min(−1), p<0.05) or ivabradine alone (312.0 ±30.2 min(−1) vs. 350.2 ±16.0 min(−1), p<0.05); (329.8 ±24.2 min(−1) vs. 363.0 ±21.7 min(−1), p<0.05). CONCLUSIONS: Concomitant administration of simvastatin with ivabradine intensified slowing of HR, although it did not influence BP in normo-and hypercholesterolemic rats. Statin-induced intensification of HR deceleration after metoprolol administration was not observed. Termedia Publishing House 2012-07-04 2012-07-04 /pmc/articles/PMC3400921/ /pubmed/22852014 http://dx.doi.org/10.5114/aoms.2012.29411 Text en Copyright © 2012 Termedia & Banach http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported License, permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Experimental Research
Owczarek, Jacek
Jasińska, Magdalena
Drożdż, Jarosław
Orszulak-Michalak, Daria
Concomitant administration of simvastatin with ivabradine in contrast to metoprolol intensifies slowing of heart rate in normo- and hypercholesterolemic rats
title Concomitant administration of simvastatin with ivabradine in contrast to metoprolol intensifies slowing of heart rate in normo- and hypercholesterolemic rats
title_full Concomitant administration of simvastatin with ivabradine in contrast to metoprolol intensifies slowing of heart rate in normo- and hypercholesterolemic rats
title_fullStr Concomitant administration of simvastatin with ivabradine in contrast to metoprolol intensifies slowing of heart rate in normo- and hypercholesterolemic rats
title_full_unstemmed Concomitant administration of simvastatin with ivabradine in contrast to metoprolol intensifies slowing of heart rate in normo- and hypercholesterolemic rats
title_short Concomitant administration of simvastatin with ivabradine in contrast to metoprolol intensifies slowing of heart rate in normo- and hypercholesterolemic rats
title_sort concomitant administration of simvastatin with ivabradine in contrast to metoprolol intensifies slowing of heart rate in normo- and hypercholesterolemic rats
topic Experimental Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400921/
https://www.ncbi.nlm.nih.gov/pubmed/22852014
http://dx.doi.org/10.5114/aoms.2012.29411
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