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 .