After heart rate and blood pressure assessment, 0.25 ml of blood samples were taken for further lipid profile examination. rate and blood pressure (mean, systolic, diastolic) were similar as compared to the group receiving metoprolol alone. Conclusions Simvastatin administration during a 4-week period in different doses did not influence the heart rate or blood pressure after metoprolol injection in normocholesterolaemic and normotensive rats. strong class=”kwd-title” Keywords: rats, simvastatin, metoprolol, heart rate, blood pressure Introduction Nowadays 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) inhibitors are the most important drugs used in the primary and secondary prevention of cardiovascular events. Their beneficial activity is dependent on limiting cholesterol synthesis; therefore current guidelines recommend aggressive cholesterol lowering with statins. Dose-dependent side effects of statins involving myopathy and alteration of cell membrane are observed, as well [1, 2]. On the other hand, cholesterol-independent pleiotropic effects of statins have been reported . In some cases, to obtain target low-density lipoproteins (LDL)-C, statins are co-administered with other lipid-lowering agents . From a practical viewpoint, monotherapy with HMG-CoA inhibitors is applied; the statin dosage used by patients might be enlarged, however. In therapy, statins are often applied with 1-blockers such Dehydrocostus Lactone as metoprolol. In the previous study it was shown that simvastatin influenced the heart rate and blood pressure after metoprolol administration . Mlh?user em et al /em . showed that atorvastatin desensitized 1-adrenergic signalling by reducing isoprenylation of G-protein . This interaction was dependent on both the drug concentration and drug administration period. In our previous study simvastatin after 2 weeks of administration to normocholesterolaemic and normotensive rats did not influence the heart rate or blood pressure after bolus injection of metoprolol [7, 8]. The aim of the study was to evaluate the influence of bolus injection of metoprolol after Dehydrocostus Lactone 4-week administration of simvastatin given at different doses on the heart rate and blood pressure. Material and methods Animals The study was approved by the Ethics Committee of the Medical University of Lodz (Poland) C 43/?B300-Az/2006. The experiments were performed in 51 8-11-week-old anaesthetized Wistar rats, outbred males. A several-day adaptation period was scheduled prior to the beginning of the experiment. After the adaptation period, animals were divided into 8 groups receiving: 1) 0.2% methylcellulose, intragastrically (ig); 2) 0.2% methylcellulose (ig) and metoprolol at 5 mg/kg body wieght (bw) intraperitoneally (ip); 3) simvastatin at 1 mg/kg bw (ig); 4) simvastatin at 10 mg/kg bw (ig); 5) simvastatin at 20 mg/kg bw (ig); 6) simvastatin at 1 mg/kg bw (ig)+metoprolol at 5 mg/kg bw (ip); 7) simvastatin at 10 mg/kg bw (ig)+metoprolol at 5 mg/kg bw (ip); 8) simvastatin at 20 mg/kg bw (ig)+metoprolol at 5 mg/kg bw (ip). Simvastatin (Polfarmex, Poland series no. KY-SI-M20030102) or placebo (0.2% methylcellulose) were given ig over a 4-week period. Rats had free access to standard diet (granulated mix LSK) and water. After administration of drugs or vehicle, heart rate and haemodynamic parameters were measured. The Rabbit Polyclonal to S6K-alpha2 surgery was performed 24 h after administration of the last drug dose and 10 h after the last feed supply. For further surgical procedures, anaesthesia was initiated by an ip dose of pentobarbital sodium at 60 mg/kg bw. The anaesthesia was maintained by intraperitoneal bolus injections of pentobarbital sodium at 10 mg/kg bw, as needed. For the measurement of heart rate and blood pressure, catheters were implanted into the right carotid artery. The signals were provided by an Isotec pressure transducer connected Dehydrocostus Lactone to a direct current bridge amplifier (both Hugo Sachs Elektronik). After the haemodynamic stabilization period (about 15 min), an intraperitoneal single injection of metoprolol at 5 mg/kg bw or 0.9% NaCl (2 ml/100 g bw) was administered. After heart rate and blood pressure assessment, 0.25 ml of blood samples were taken for further lipid profile examination. Surgical procedures, heart rate and blood.