Effect of Telmisartan in amelioration inflammatory Responses Induced by Myocardial Ischemia/Reperfusion Injury IN male Mice

Abstract

Background: Myocardial ischemia–reperfusion represents a clinically relevant problem associated with thrombolysis, angioplasty and coronary bypass surgery. Angiotensin II may contribute to reperfusion injury by increasing oxidative stress and inflammatory factors . Ang II exerts most of its effects via AT1Rs. Apoptosis of cardiomyocytes may further be influenced by Ang II. Objective: This study was undertaken to investigate the potential role of Telmisartan in amelioration of myocardial I/R injury induced by ligation of coronary artery in mouse model. Materials & method: Adult male Swiss-albino mice were randomized into 4 equal groups. Group (1) sham group: Mice underwent the same anesthetic and surgical procedure as the active control group except ligation of LAD coronary artery.Group( 2) active control group: Mice were subjected to regional ischemia for 30 min by ligation of LAD coronary artery and reperfusion for 2 hours .Group( 3) control vehicle group (1): Mice in this group injected with DMSO (vehicle for Telmisartan ) via IP route & underwent Myocardial ischemia for 30 minutes by ligation of (LAD) coronary artery & reperfusion for 2 hr . Group (4)Telmisartan treated group : Mice pretreated with Telmisartan 0.5mg/kg i.p 30 minutesbefore ligation of LAD coronary artery. Results: Compared with the sham group, Levels of TNF-α & IL-1β, IL-6,caspase 3 and plasma level of cardiac troponin I increased in control group (p<0.001).Levels of Bcl2 decreased in control group(p<0.001). Histologically ,All mice in control group showed a significant (p<0.001) cardiac injury. Telmisartan significantly counteract the increase in myocardium level of TNF-α, IL-1B,IL-6,caspase 3 ,plasma cTnI (P < 0.001). Furthermore, the Telmisartan significantly increased in myocardium level of Bcl2. Histological analysis revealed that both Telmisartan markedly reduced (P < 0.001) the severity of cardiac injury in the mice underwent LAD ligation procedure . Conclusion:The results of the present study reveal that Telmisartan may ameliorate myocardial I/R injury in Male Mice via interfering with inflammatory reactions & apoptosis which induced by I/R injury .