Exogenous GalR2‐specific peptide agonist as a tool for treating myocardial ischemia/reperfusion injury

Abstract

AbstractObjectives: The aim of this work was to elucidate the role of GalR2 receptor activation in protecting the rat heart in vivo from ischemia/reperfusion (I/R) damage by a pharmacological peptide agonist WTLNSAGYLLGPβAH‐OH (G1) and full‐length rat galanin GWTLNSAGYLLGPHAIDNHRSFSDKHGLT‐NH2 (G2) using M871, a selective inhibitor of GalR2. Methods: The peptides were prepared by the automatic solid‐phase synthesis using the Fmoc‐strategy and purified by high‐performance liquid chromatography (HPLC). A 40‐min left anterior descending (LAD) coronary artery occlusion followed by a 60‐min reperfusion was performed. The criteria for damage/protection of the heart were the infarct size (IS) and plasma activity of creatine kinase‐MB (CK‐MB) at the end of reperfusion. Results: Intravenous injection of G1 or G2 at an optimal dose of 1 mg/kg at the fifth minute of reperfusion significantly reduced the IS (by 35% and 32%, respectively) and activity of CK‐MB at the end of reperfusion (by 43% and 38%, respectively) compared with the control. Administration of M871 (8 mg/kg) 5 min before the onset of reperfusion abolished the effects of G1 on IS and CK‐MB activity, returning them to control values. Co‐administration of M871 (8 mg/kg) with G2 attenuated protective effect of G2 on both IS and plasma СK‐MB activity. However, differences in these parameters between the M871+G2 and G2 groups did not reach statistical significance (P = 0.139 and P = 0.121, respectively). Conclusion: Thus, GalR2 is the principal receptor subtype that transduces the protective effects of galanin and ligand G1 in myocardial I/R injury. This suggests that GalR2‐specific peptide agonists could be used as drug candidates for treating ischemic heart disease.