Protective effects of amlodipine, coenzyme Q10 and their combination on myocardial ischemia/reperfusion injury in rats

ABSTRACT

Ischemia/reperfusion [I/R] injury is of major clinical relevance during ischemic heart diseases, percutaneous transluminal angioplasty, coronary artery bypass and heart transplantation. Amlodipine, a calcium channel blocker, exhibits antioxidant and antiproliferative activities as well as eNOS activation that could help in cardioprotection following I/R insult. Coenzyme Q10 [CoQ], a mitochondrial coenzyme involved in oxidative phosphorylation, possesses strong antioxidant and lipid peroxyl neutralizing functions. The current study demonstrated the possible cardioprotection of amlodipine [15 mg/kg/day] and CoQ [200 mg/kg/day] alone or in combination against myocardial I/R-induced functional, metabolic and cellular changes. Drugs were administered orally for one week. Rats were then subjected to myocardial I/R [35min/10min]. Heart rates and incidence of ventricular arrhythmias were recorded during l/R progress. At the end of reperfusion, blood samples were collected for estimation of plasma creatine kinase [CK] activity. The left ventricle homogenates were used for determination of lactate, ATP, thiobarbituric acid reactive substances [TBARS], reduced glutathione [GSH] and total nitrate/nitrite [NOx] contents as well as myeloperoxidase [MPO] activity. Finally, histological examination was performed to visualize the possible cellular effects of the drugs. Amlodipine, CoQ and their combination significantly protected against reperfusion-induced tachycardia and decreased the incidence and severity of arrhythmias. Amlodipine afforded a significant degree of protection against plasma CK elevation and myocardial GSH depletion, while it completely protected against myocardial MPO, lactate and TBARS elevation. On the other hand, it failed to defend against ATP depletion and NOx elevation. CoQ provided a significant degree of protection against plasma CK, myocardial MPO, NOx elevation and ATP depletion. It completely protected against GSH depletion, lactate and TBARS elevation. Combination therapy provided significant increase in myocardial ATP and GSH contents and significant decrease in plasma CK activity in comparison with amlodipine monotherapy. It could be concluded that adding CoQ to amlodipine therapy offered remarkable improvement in the cardioprotective effect of amlodipine