EFFECTS OF ROSUVASTATIN IN EXPERIMENTALLY-INDUCED CARDIAC ISCHEMIA AND ON AORTIC VASCULAR REACTIVITY.

Document Type : Original Article

Author

Department of Pharmacology , Faculty of Medicine , Al-Az har University, Cairo

Abstract

Myocardial infarction (MI) continues to be a major public health problem in the world. The present study aimed to elucidate the protective effect of  different doses  of rosuvastatin and cilostazol, as well as their combination on isoprenaline-induced MI in rats as well as their effects on isolated aorta. Methods: I- Adult rats received different doses of rosuvastatin (1,2,5,10, & 20mg/kg), cilostazol (18mg/kg) and combination of rosuvastatin 1mg/kg and cilostazol 18mg/kg by oral gavage daily for 16 days, then rats  were subcutaneously injected with two doses 24-h apart of 150mg/kg isoprenaline in the last two days. ECG pattern was monitored, myocardial injury markers (CK-MB and LDH) and inflammatory biomarker  (CRP) were measured in serum. MDA, catalase and SOD were quantified in cardiac homogenates and heart tissue damage was examined by histopathology. II- Effects of rosuvastatin (0.2 µg/ml – 6.4 µg/ml), cilostazol (7.5 µg/ml – 480 µg/ml) and combination  cilostazol (30 µg/ml) and rosuvastatin (0.2 µg/ml – 6.4 µg/ml) on NE-induced contraction in rabbit aortic strip were recorded. Each dose of either rosuvastatin or cilostazol were incubated for 10 min and 15min respectively  then NE (0.5 µg/ml) was added and the contraction was recorded for one and half min. Results: I- Pretreatment with different doses of rosuvastatin (1,2,5 & 10), cilostazol 18mg/kg and the combination markedly ameliorated ISO-induced alterations in ECG, cardiac markers, inflammatory marker, oxidative markers and heart architecture. However, protection disappeared at higher dose of rosuvastatin 20mg/kg. II- Addition of either rosuvastatin (0.2-6.4 µg/ml), cilostazol (7.5-480µg/ml) or combination rosuvastatin (0.2-6.4 µg/ml) and cilostazol 30µg/ml produced a significant decrease in the height of NE-induced contraction in a dose dependent manner. Conclusion:  I-This study provides evidence that rosuvastatin,  cilostazol and their combination possess cardioprotective effect on isoprenaline-induced myocardial infarction. II- The drugs had vasorelaxant effect on aorta. Mechanism of drug action are discussed.

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