Protection of the myocardium against ischemia/reperfusion injury by angiotensin-(1–9) through an AT 2 R and Akt-dependent mechanism

Evelyn Mendoza-Torres, Jaime A. Riquelme, Alejandra Vielma, Andrea Ramirez Sagredo, Luigi Gabrielli, Roberto Bravo-Sagua, Jorge E. Jalil, Beverly A. Rothermel, Gina Sanchez, Maria Paz Ocaranza, Sergio Lavandero

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Angiotensin-(19), a peptide of the non-classical renin angiotensin system, has been shown to prevent and revert hypertension and cardiac hypertrophy. We hypothetized that systemic delivery of angiotensin-(1–9) following myocardial infarction will also be protective and extend to provide protection during reperfusion of the ischemic heart. Adult Sprague Dawley rats were subjected to left anterior descending artery ligation and treated with angiotensin-(1–9) via osmotic mini-pump for 2 weeks in the presence or absence of Mas receptor or AT 2 R antagonists (A779 and PD123319, respectively). Myocardial death and left ventricular function were evaluated after infarction. Infarct size and functional parameters were determined in isolated rat hearts after global ischemia/reperfusion in the presence of angiotensin-(1–9) plus receptor antagonists or Akt inhibitor at reperfusion. in vitro, neonatal rat ventricular cardiomyocytes underwent simulated ischemia/reperfusion and angiotensin-(1–9) was co-incubated with A779, PD123319 or Akt inhibitor. Systemic delivery of angiotensin-(1–9) significantly decreased cell death and improved left ventricular recovery after in vivo myocardial infarction. Perfusion with the peptide reduced the infarct size and improved functional recovery after ex vivo ischemia/reperfusion. In vitro, angiotensin-(1–9) decreased cell death in isolated neonatal rat ventricular cardiomyocytes subjected to simulated ischemia/reperfusion. The cardioprotective effects of angiotensin-(1–9) were blocked by PD123319 and Akti VIII but not by A779. Angiotensin-(1–9) limits reperfusion-induced cell death by an AT 2 R- and Aktdependent mechanism. Angiotensin-(1–9) is a novel strategy to protect against cardiac ischemia/reperfusion injury.

Original languageEnglish (US)
Pages (from-to)112-121
Number of pages10
JournalPharmacological Research
StatePublished - Sep 2018


  • 2,3,5-Triphenyltetrazolium chloride (CID: 9283)
  • 2-deoxy-D-glucose (CID: 108223)
  • A779 (CID: 10169886)
  • Akt inhibitor VIII (CID: 10196499)
  • Angiotensin type 2 receptor
  • Angiotensin-(1–9)
  • Angiotensin-(1–9) (CID: 71745056)
  • Cardioprotection
  • Heparin (CID: 772)
  • Lactic acid (CID: 329761959)
  • PD123319 (CID: 5311345)
  • Pentobarbital (CID: 4737)
  • Propidium iodide (CID: 104981)
  • Renin-angiotensin system
  • ischemia/reperfusion

ASJC Scopus subject areas

  • Pharmacology


Dive into the research topics of 'Protection of the myocardium against ischemia/reperfusion injury by angiotensin-(1–9) through an AT 2 R and Akt-dependent mechanism'. Together they form a unique fingerprint.

Cite this