title: Ang-(1-7) offers cytoprotection against ischemia-reperfusion injury by restoring intracellular calcium homeostasis.
abstract: Accumulating evidence indicates that angiotensin-(1-7) [Ang-(1-7)] offers protective effects against ischemia-reperfusion (I/R) induced arrhythmias and contractile dysfunction, which are related to disturbances of intracellular calcium homeostasis. However, whether or not Ang-(1-7) regulates intracellular calcium in I/R is not clear. To shed light on this issue, we carried out studies with a cellular model of simulated I/R in isolated rat ventricular myocytes and measured calcium transients using laser scanning confocal microscopy. Our results showed that Ang-(1-7) had no effects on the calcium transient in myocytes superfused with normal solution; however, in myocytes of simulated I/R, Ang-(1-7) significantly attenuated the increased diastolic intracellular Ca during reperfusion, restored the decreased peak Ca of calcium transient during ischemia, and reversed the decreased amplitude of calcium transient throughout the I/R periods. Additionally, Ang-(1-7) significantly suppressed the reactive oxygen species production in I/R, especially during the ischemic phase. These data indicated that Ang-(1-7) affords significant cytoprotective effects through directly improving calcium homeostasis independent of its anti-oxidative action. Most notably, the effects of Ang-(1-7) on intracellular Ca dynamics manifests only in the diseased states, that is, I/R. This unique property suggests that upregulation of Ang-(1-7) expression and/or activation of the Ang-(1-7)/Mas signaling cascade is a highly desirable strategy for the treatment of myocardial impairment induced by I/R.
authors.affiliation: *Department of Cardiology, The First Affiliated Hospital; Sun Yat-Sen University, Guangzhou, China; †Department of Cardiology, The Third People's Hospital of Chengdu, Sichuan, China; ‡Department of Physiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China; and §Department of Physiology, Guangzhou Medical University, Guangzhou, China.
authors.forename: Lichun
authors.initials: L
authors.lastname: Wang
authors.forename: Duan
authors.initials: D
authors.lastname: Luo
authors.forename: Xinxue
authors.initials: X
authors.lastname: Liao
authors.forename: Jiangui
authors.initials: J
authors.lastname: He
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.forename: Chuntao
authors.initials: C
authors.lastname: Yang
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D019610:Cytoprotection / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D008297:Male; D018613:Microscopy, Confocal; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D010446:Peptide Fragments; D000803:Angiotensin I; C118790:angiotensin I (1-7); D002118:Calcium