title: Cellular basis of angiotensin-(1-7)-induced augmentation of left ventricular functional performance in heart failure.
abstract: BACKGROUND
  Angiotensin-(1-7) [Ang-(1-7)] exhibits cardiovascular effects opposite those of angiotensin II (Ang II), thus providing protection against heart disease. However, how Ang-(1-7) imparts cardioprotection is unclear, and its direct cardiac effects are controversial. Whether heart failure (HF) alters cardiac contractile responses to Ang-(1-7) remains undetermined. We tested the hypothesis that in HF, Ang-(1-7) may produce positive modulation on [Ca2+]iregulation, enhancing left ventricular (LV) and myocyte contraction and relaxation via Ang-(1-7) Mas receptor coupled with nitric oxide (NO)/bradykinin (BK)-mediated mechanism.
  
  
  RESULTS
  We measured LV contractility changes after Ang-(1-7) (650ng/kg, iv) and compared myocyte functional and [Ca2+]itransient ([Ca2+]iT) responses to Ang-(1-7) superfusion in 24 normal rats and 34 rats with isoproterenol-induced HF (3months after 170mg/kg, s.q. for 2days). To assess the mechanisms of altered HF responses to Ang-(1-7), subsets of HF myocytes were pretreated to inhibit NO synthase (L-NAME), BK (HOE-140), and Mas receptor (A-779) followed with Ang-(1-7). In normal rats, Ang-(1-7) produced no significant changes in LV and myocyte function. In HF rats, Ang-(1-7) significantly augmented LV contractility and relaxation with increased EES(51%), but decreased τ compared to baseline. Ang-(1-7) also significantly increased myocyte contraction (dL/dtmax, 30%), relaxation (dR/dtmax, 41%), and [Ca2+]iT. L-NAME increased, HOE-140 decreased, and A-779 prevented HF myocyte contractile responses to Ang-(1-7).
  
  
  CONCLUSIONS
  In a rat model of HF, Ang-(1-7) increases [Ca2+]iT, and produces positive inotropic and lusitropic effects in the LV and myocytes. These effects are mediated by the Mas receptor and involve activation of NO/BK pathways.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Section on Cardiovascular Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United States.
authors.forename: Heng-Jie
authors.initials: HJ
authors.lastname: Cheng
authors.affiliation: Section on Cardiovascular Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United States.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Section on Cardiovascular Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United States.
authors.forename: Dalane W
authors.initials: DW
authors.lastname: Kitzman
authors.affiliation: Department of Surgery, Wake Forest School of Medicine, Winston-Salem, NC, United States; Department of Internal Medicine-Nephrology, Wake Forest School of Medicine, Winston-Salem, NC, United States; Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, United States.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Ferrario
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address: liweimin_2009@163.com.
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Li
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China; Section on Cardiovascular Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United States. Electronic address: ccheng@wakehealth.edu.
authors.forename: Che Ping
authors.initials: CP
authors.lastname: Cheng
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use; D016277:Ventricular Function, Left / Q000187:drug effects* / Q000502:physiology
chemical_list: D010446:Peptide Fragments; D014665:Vasodilator Agents; D000803:Angiotensin I; C118790:angiotensin I (1-7)
keywords: Angiotensin-(1-7); Calcium transient; Cells; Contractility; Heart failure; Pressure-volume relation