title: AT1 Receptor Modulator Attenuates the Hypercholesterolemia-Induced Impairment of the Myocardial Ischemic Post-Conditioning Benefits.
abstract: OBJECTIVE
  Ischemic post-conditioning (PostC) has been demonstrated as a novel strategy to harness nature's protection against myocardial ischemia-reperfusion (I/R). Hypercholesterolemia (HC) has been reported to block the effect of PostC on the heart. Angiotensin II type-1 (AT1) modulators have shown benefits in myocardial ischemia. The present study investigates the effect of a novel inhibitor of AT1, azilsartan in PostC of the heart of normocholesterolemic (NC) and HC rats.
  
  
  METHODS
  HC was induced by the administration of high-fat diet to the animals for eight weeks. Isolated Langendorff's perfused NC and HC rat hearts were exposed to global ischemia for 30 min and reperfusion for 120 min. I/R-injury had been assessed by cardiac hemodynamic parameters, myocardial infarct size, release of tumor necrosis factor-alpha troponin I, lactate dehydrogenase, creatine kinase, nitrite in coronary effluent, thiobarbituric acid reactive species, a reduced form of glutathione, superoxide anion, and left ventricle collagen content in normal and HC rat hearts.
  
  
  RESULTS
  Azilsartan post-treatment and six episodes of PostC (10 sec each) afforded cardioprotection against I/R-injury in normal rat hearts. PostC protection against I/R-injury was abolished in HC rat hearts. Azilsartan prevented the HC-mediated impairment of the beneficial effects of PostC in I/R-induced myocardial injury, which was inhibited by L-N5-(1-Iminoethyl)ornithinehydrochloride, a potent inhibitor of endothelial nitric oxide synthase (eNOS).
  
  
  CONCLUSIONS
  Azilsartan treatment has attenuated the HC-induced impairment of beneficial effects of PostC in I/R-injury of rat hearts, by specifically modulating eNOS. Azilsartan may be explored further in I/R-myocardial injury, both in NC and HC conditions, with or without PostC.
authors.affiliation: Department of Cardiology, Henan University Huaihe Hospital, Henan, China.
authors.forename: Yun-Wei
authors.initials: YW
authors.lastname: Li
authors.affiliation: Department of Cardiology, Henan University Huaihe Hospital, Henan, China.
authors.forename: Yan-Ming
authors.initials: YM
authors.lastname: Li
authors.affiliation: Department of Cardiology, Henan University Huaihe Hospital, Henan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Hon
authors.affiliation: Department of Cardiology, Henan University Huaihe Hospital, Henan, China.
authors.forename: Qi-Lin
authors.initials: QL
authors.lastname: Wan
authors.affiliation: Department of Cardiology, Henan University Huaihe Hospital, Henan, China.
authors.forename: Rui-Li
authors.initials: RL
authors.lastname: He
authors.affiliation: Department of Cardiology, Henan University Huaihe Hospital, Henan, China.
authors.forename: Zhi-Zhong
authors.initials: ZZ
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Henan University Huaihe Hospital, Henan, China.
authors.forename: Cui-Hua
authors.initials: CH
authors.lastname: Zhao
keywords: AT1 receptor blocker; Azilsartan; Ischemia-reperfusion injury; myocardial infarction