Endogenous angiotensin-(1-7)/Mas receptor/NO pathway mediates the cardioprotective effects of pacing postconditioning.

Abstract

The aim of the present study was to investigate the role of the ANG-(1-7) receptor (Mas) and nitric oxide (NO) in pacing postconditiong (PPC)-mediated cardioprotection against ischemia-reperfusion injury. Cardiac contractility and hemodynamics were assessed using a modified Langendorff system, cardiac damage was assessed by measuring infarct size and creatinine kinase levels, and levels of phosphorylated and total endothelial NO synthase (eNOS) were determined by Western blot analysis. Isolated hearts were subjected to 30 min of regional ischemia, produced by fixed position ligation of the left anterior descending coronary artery, followed by 30 min of reperfusion (n = 6). Hearts were also subjected to PPC (three cycles of 30 s of left ventricular pacing alternated with 30 s of right atrial pacing) and/or treated during reperfusion with ANG-(1-7), N(G)-nitro-l-arginine methyl ester, or the Mas antagonist (d-Ala7)-ANG I/II (1-7). The PPC-mediated improvement in cardiac contractility and hemodyanamics, cardiac damage, and eNOS phosphorylation were significantly attenuated upon treatment with (d-Ala7)-ANG I/II (1-7) or N(G)-nitro-l-arginine methyl ester. Treatment with ANG-(1-7) improved cardiac function and reduced infarct size and creatinine kinase levels; however, the effects of ANG-(1-7) were not additive with PPC. In conclusion, these data provide novel insights into the cardioprotective mechanisms of PPC in that they involve the Mas receptor and eNOS and further suggest a potential therapeutic role for ANG-(1-7) in cardiac ischemic injury.

• Authors: Ala'a Abwainy, Fawzi Babiker, Saghir Akhtar, Ibrahim F Benter
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 310 Issue 1 Pg. H104-12 (Jan 01 2016) ISSN: 1522-1539 [Electronic] United States
• PMID: 26519026 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 the American Physiological Society.

Chemical References

• Enzyme Inhibitors
• Peptide Fragments
• Proto-Oncogene Mas
• Proto-Oncogene Proteins
• Receptors, G-Protein-Coupled
• Nitric Oxide
• Angiotensin I
• Nitric Oxide Synthase Type III
• Nos3 protein, rat
• Creatine Kinase
• angiotensin I (1-7)

Topics

• Angiotensin I (metabolism, pharmacology)
• Animals
• Cardiac Pacing, Artificial (methods)
• Creatine Kinase (metabolism)
• Enzyme Inhibitors (pharmacology)
• Hemodynamics
• Isolated Heart Preparation
• Male
• Myocardial Contraction
• Myocardial Infarction (metabolism, pathology, physiopathology, prevention & control)
• Myocardial Reperfusion Injury (metabolism, pathology, physiopathology, prevention & control)
• Myocardium (metabolism, pathology)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type III (antagonists & inhibitors, metabolism)
• Peptide Fragments (metabolism, pharmacology)
• Phosphorylation
• Proto-Oncogene Mas
• Proto-Oncogene Proteins (drug effects, metabolism)
• Rats, Wistar
• Receptors, G-Protein-Coupled (drug effects, metabolism)
• Signal Transduction
• Time Factors
• Ventricular Function, Left (drug effects)