Aliskiren Protects Against Myocardial Ischaemia- Reperfusion Injury Via An Endothelial Nitric Oxide Synthase Dependent Manner

Background Heart ischemic disease is a kind of disease that endangers human life and health,among which,hypertension and coronary heart disease constitute its main part.The normal shape of the heart structure,function and metabolism rely on coronary perfusion.Cardiac muscle cells under normal physiological condition have strong tolerance of short ischemia.Coronary arteries as the nutrient vessels of the heart provide the needed energy and oxygen for the myocardial cell.However,when coronary perfusion continues to be lacking,the myocardium cannot maintain a normal physiological environment.In the condition of continuous ischemia,ATP level drops rapidly,which leads to cardiac metabolic disorders,myocardial infarction,structural damage,and even functional impairment,which is the occurrence of ischemic injury.To cure the cardiac ischemia,the most important is to restore heart perfusion.Timely preventing ischemic injury,stopping further development of the damage of myocardial cell and recovering its normal function,as the final purposes.However,with ischemic myocardial blood flow recovery,reperfusion injury occurs,namely ischemia reperfusion injury.Ischemia reperfusion injury is a complex pathophysiological process,including calcium overload,oxygen free radical,endothelial and neutrophils interaction,and apoptosis.Objective Aliskiren,direct renin inhibitor,can block the RAS activation,in theory it can avoid vascular converting enzyme inhibitors and angiotensin Ⅱ receptor blockers.We found that aliskiren can obviously dilating thoracic aorta through e NOS gene.In this study,we try to prove the protection of aliskiren in myocadial ischemia-reperfusion injury through e NOS gene.Method Wild type mice and eNOS^-/-mice were respectively and randomly divided into alis50 group and vechile group,four groups in common,each group contains 8 mice.Baseline blood pressure were recorded.After that mice were treated with Aliskiren for four weeks,and blood pressure were measured weekly.Then,mice models of cardiac ischemia-reperfusion were built.Finally,plasma renin activity,angiotensin Ⅱ content,heart function,EF,FS,plasma CK activity,LDH activity,MDA,T-AOC,T-SOD were measured.Result1.Aliskiren could significantly reduce the blood pressure of e NOS gene knockout mice since the third week,also,could reduce mice renin activity and angiotensin Ⅱ content in eNOS^-/-mice and WT mice.2.There was no significant improvement in cardiac function after the e NOS gene knockout of the mice pretreated with aliskiren,while the cardiac function of the wild type mice pretreated with aliskiren was significantly improved.3.Oxidative stress and anti-oxidative stress indicators in eNOS^-/-mice had no significant difference between group Alis50 and group Vechile.Alisiren could obviously reduce oxidative stress indicators in WT mice.Conclusion we clarified the Aliskiren in cardiac ischemia reperfusion injury of important protection,has been clear about the endothelial nitric oxide synthase signal pathway mediated Aliskiren heart protection.