Interaction between different doses of simvastatin after two-week administration and metoprolol injection on the heart rate in normocholesterolemic rats.
Heart rate slowing is the beneficial effect after beta-blocker administration in cardiac heart failure and ischemic heart disease. However, bradycardia and another cardiac disturbances after beta-blockers therapy are the most dangerous side effects. Many patients with cardiovascular diseases receiving beta-blockers are recommended to statin therapy, as well. Previous study showed that statins may desensitize beta-adrenergic signaling, in cardiac myocytes via reduction of isoprenylation of G-protein gamma-subunits. The aim of the study was to evaluate the influence of simvastatin at different doses and metoprolol injection on the heart rate in normocholesterolemic rats. The experiments were performed in Wistar rats, outbred males. Simvastatin at 1, 10 or 20 mg/kg or vehicle (0.2% methylcellulose) were given intragastrically during two-week period. After two week administration of simvastatin, rats were injected intraperitoneally with metoprolol at 5 mg/kg b.w. The heart rate signals were provided by Isotec pressure transducer connected to a direct current bridge amplifier and catheter was implanted into the right carotid artery. No changes in the baseline heart rate among all groups of the animals were observed. Metoprolol administration caused statistically significant decrease in heart rate in all groups of rats. In the control group, after metoprolol administration heart rate slowed down to 83.11 +/- 1.11% (p < 0.05) of the baseline values, in group receiving simvastatin at 1 mg/kg b.w. 82.72 +/- 5.49% (p < 0.05), in group receiving simvastatin at 10 mg/kg b.w. 85.13 +/- 4.75 (p <0.05) and in group receiving simvastatin at 20 mg/kg b.w. 85.13 +/- 4,75% (p < 0.05) of the baseline values. No significant decrease in heart rate in the control group as compared to groups receiving simvastatin in different doses was observed. No significant changes among animals receiving simvastatin in different doses were observed, as well.


CONCLUSIONS
Two week administration of simvastatin in different doses to normocholesterolaemic rats does not modify metoprolol-induced depressing influence on the heart rate.
Department of Biopharmacy, Medical University of Łódź, Poland. jacow2@tlen.pl
Jacek
J
Owczarek
Magdalena
M
Jasińska
Daria
D
Orszulak-Michalak
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D008747:Methylcellulose / Q000737:chemistry; D008790:Metoprolol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008747:Methylcellulose; D019821:Simvastatin; D008790:Metoprolol