Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012:2012:976519.
doi: 10.1100/2012/976519. Epub 2012 May 3.

Concomitant administration of different doses of simvastatin with ivabradine influence on PAI-1 and heart rate in normo- and hypercholesterolaemic rats

Jacek Owczarek  1 , Magdalena Jasińska-Stroschein, Daria Orszulak-Michalak
Affiliations

Concomitant administration of different doses of simvastatin with ivabradine influence on PAI-1 and heart rate in normo- and hypercholesterolaemic rats

Jacek Owczarek et al. ScientificWorldJournal. 2012.

Abstract

Ivabradine is a novel heart rate lowering agent that inhibits I(f) ionic current in the sinus node and demonstrates antiischaemic and antianginal activity. The aim of the paper was to investigate the effect its dose-dependent drug-drug interaction with simvastatin inhibitor HMGCo-A has on PAI-1 blood level, heart rate and blood pressure. The experiments were performed in hyper- and normocholesterolemic Wistar rats receiving simvastatin (1 and 20 mg × kg(-1) bw) with ivabradine (10 mg × kg(-1) bw) during a 4-week period. Ivabradine exacerbated the decrease of PAI-1 in normocholesterolemic animals receiving simvastatin at a dose of 1 mg/kg bw and was not observed to have any significant influence on the PAI-1 values in rats receiving 20 mg × kg(-1) bw simvastatin. Ivabradine, coadministered with simvastatin given at a dose of 20 mg × kg(-1) bw, significantly slowed the heart rate in normocholesterolaemic and hypercholesterolaemic groups as compared to the group receiving ivabradine alone. Conclusion. The administration of ivabradine to normocholesterolaemic and hypercholesterolaemic rats receiving simvastatin significantly exacerbated the slowing of heart rate with no effect on blood pressure. The administration of ivabradine has been shown to demonstrate different effects on PAI-1 values depending on lipid disorders.

PubMed Disclaimer

Figures

Figure 1
Figure 1
PAI–1 blood level (ng/mL) in Wistar rats fed normocholesterolaemic diet. K_N: normocholesterolaemic control group, IW_N: normocholesterolaemic group receiving ivabradine, S1_N: normocholesterolaemic group receiving simvastatin at a dose of 1 mg × kg−1 bw, S20_N: normocholesterolaemic group receiving simvastatin at a dose of 20 mg × kg−1 bw, IW_N_S1: normocholesterolaemic group receiving ivabradine and simvastatin at a dose of 1 mg × kg−1 bw, IW_N_S20: normocholesterolaemic group receiving ivabradine and simvastatin at a dose of 20 mg × kg−1 bw, *P < 0.05 as compared to the control group, (a) P < 0.05 as compared to rats receiving simvastatin alone, and (b) P < 0.05 as compared to rats receiving ivabradine alone.
Figure 2
Figure 2
PAI–1 level (ng/mL) in Wistar rats fed hypercholesterolaemic diet. K_H: hypercholesterolaemic control group, IW_H: hypercholesterolaemic group receiving ivabradine, S1_H: hypercholesterolaemic group receiving simvastatin at a dose of 1 mg × kg−1 bw, S20_H: hypercholesterolaemic group receiving simvastatin at a dose of 20 mg × kg−1 bw, IW_H_S1: hypercholesterolaemic group receiving ivabradine and simvastatin at a dose of 1 mg × kg−1 bw, IW_H_S20: hypercholesterolaemic group receiving ivabradine and simvastatin at a dose of 20 mg × kg−1 bw, *P < 0.05 as compared to the control group, and (a) P < 0.05 as compared to rats receiving simvastatin alone.
Figure 3
Figure 3
Resting mean heart rate (min−1) in Wistar rats fed normocholesterolaemic diet. K_N: normocholesterolaemic control group, IW_N: normocholesterolaemic group receiving ivabradine, S1_N: normocholesterolaemic group receiving simvastatin at a dose of 1 mg × kg−1 bw, S20_N: normocholesterolaemic group receiving simvastatin at a dose of 20 mg × kg−1 bw, IW_N_S1: normocholesterolaemic group receiving ivabradine and simvastatin at a dose of 1 mg × kg−1 bw, IW_N_S20: normocholesterolaemic group receiving ivabradine and simvastatin at a dose of 20 mg × kg−1 bw, *P < 0.05 as compared to the control group, (a)  P < 0.05 as compared to rats receiving simvastatin alone, (b)  P < 0.05 as compared to rats receiving ivabradine alone, and (c) P < 0.05 as compared to rats receiving ivabradine and simvastatin at a dose of 1 mg × kg−1 bw.
Figure 4
Figure 4
Resting mean heart rate (min−1) in Wistar rats fed hypercholesterolaemic diet. K_H: hypercholesterolaemic control group, IW_H: hypercholesterolaemic group receiving ivabradine, S1_H: hypercholesterolaemic group receiving simvastatin at a dose of 1 mg × kg−1 bw, S20_H: hypercholesterolaemic group receiving simvastatin at a dose of 20 mg × kg−1 bw, IW_H_S1-hypercholesterolaemic group receiving ivabradine and simvastatin at a dose of 1 mg × kg−1 bw, IW_H_S20: hypercholesterolaemic group receiving ivabradine and simvastatin at a dose of 20 mg × kg−1 bw, *P < 0.05 as compared to control group, (a) P < 0.05 as compared to rats receiving simvastatin alone, and (b) P < 0.05 as compared to rats receiving ivabradine alone, (c) P < 0.05 as compared to rats receiving ivabradine and simvastatin at a dose of 1 mg × kg−1 bw.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Kannel WB, Kannel C, Paffenbarger RS, Cupples A. Heart rate and cardiovascular mortality: the Framingham study. American Heart Journal. 1987;113(6):1489–1494. - PubMed
    1. Jouven X, Empana JP, Schwartz PJ, Desnos M, Courbon D, Ducimetière P. Heart-rate profile during exercise as a predictor of sudden death. New England Journal of Medicine. 2005;352(19):1951–1958. - PubMed
    1. Hjalmarson A, Gilpin EA, Kjekshus J, et al. Influence of heart rate on mortality after acute myocardial infarction. American Journal of Cardiology. 1990;65(9):547–553. - PubMed
    1. Custodis F, Schirmer SH, Baumhkel M, Heusch G, Bhm M, Laufs U. Vascular pathophysiology in response to increased heart rate. Journal of the American College of Cardiology. 2010;56(24):1973–1983. - PubMed
    1. Ferrari R, Cargnoni A, Ceconi C. Anti-ischaemic effect of ivabradine. Pharmacological Research. 2006;53(5):435–439. - PubMed

Publication types