Potential role of EphrinA2 receptors in postconditioning induced cardioprotection in rats.

Abstract

EphA2 receptor has emerged as a novel cardioprotective target against myocardial infarction by preserving cardiac function, limiting infarct size and inflammation and enhancing cell survival via elevating phosphorylated Akt protein levels. However, the role of Eph receptors in postconditioning remains to be elucidated. Thus, the present study was designed to explore the role of EphA2 receptors in cardioprotective mechanism of postconditioning by employing Doxazosin as EphA2 receptor agonist, Lithocholic acid as antagonist and Wortmannin as specific phosphoinositide 3-kinase (PI3K) inhibitor. In Langendorff perfused isolated rat hearts, exposure of ischemia for 30 min succeeded by reperfusion for 2 h produced cardiac damage as determined by increase in size of infarct, LVDP, liberation of LDH and CK in effluent from coronary arteries. The reperfused hearts were homogenized and tissue concentrations of TBARs, reduced GSH and Catalase were determined. A marked rise in infarct size, liberation of LDH and CK in effluent and TBARs in myocardial tissue was observed in ischemic and reperfused hearts. Ischemic postconditioning comprising of 6 alternate episodes of 10 s ischemia and 10 s reperfusion and pharmacological post-conditioning by Doxazosin infusion for 5 min Before reperfusion confers significant protection against myocardial injury as manifested by remarkably decreased infarct size, levels of LDH, CK and tissue TBARs along with increase in GSH and Catalase activity. Pre-treatment of EphA2 antagonist, Lithocholic acid and PI3K inhibitor, Wortmannin attenuated the cardioprotective effect of postconditioning. Our results suggest that EphA2 receptors may be involved in postconditioning mediated cardioprotection probably through PI3K/Akt pathway.

• Authors: Kamaldeep Kaur, Nirmal Singh, Ravi K Dhawan
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 883 Pg. 173231 (Sep 15 2020) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 32589885 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Thiobarbituric Acid Reactive Substances
• L-Lactate Dehydrogenase
• Phosphatidylinositol 3-Kinase
• Receptor, EphA2
• Proto-Oncogene Proteins c-akt
• Creatine Kinase
• Doxazosin

Topics

• Animals
• Creatine Kinase (metabolism)
• Disease Models, Animal
• Doxazosin (pharmacology)
• Female
• Hemodynamics (drug effects)
• Isolated Heart Preparation
• L-Lactate Dehydrogenase (metabolism)
• Male
• Myocardial Infarction (metabolism, pathology, physiopathology, prevention & control)
• Myocardial Reperfusion Injury (metabolism, pathology, physiopathology, prevention & control)
• Myocytes, Cardiac (drug effects, metabolism, pathology)
• Phosphatidylinositol 3-Kinase (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats, Wistar
• Receptor, EphA2 (agonists, metabolism)
• Signal Transduction
• Thiobarbituric Acid Reactive Substances (metabolism)
• Time Factors
• Ventricular Function, Left (drug effects)