Related Experiment Video
Updated: May 31, 2026
Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury
Published on: March 7, 2022
Kappa-opioid receptor activation during reperfusion limits myocardial infarction via ERK1/2 activation in isolated
June Hong Kim1, Young Ho Jang, Kook Jin Chun
1Institute of Cardiovascular Research Center, Pusan National University Yangsan Hospital, Yangsan, Korea.
Background:
We investigated whether p42/p44 extracellular signal-regulated kinases (ERK1/2) and/or phosphatidylinositol-3-OH kinase (PI3K)-Akt play a crucial role in cardioprotection by κ-opioid receptor (KOP) activation.
Methods:
Langendorff perfused rat hearts were subjected to 30 min of regional ischemia and 2 h of reperfusion. Antagonists of ERK1/2 and PI3K were perfused in hearts treated with the KOP agonist U50488H (U50). Infarct size was measured after 2 h of reperfusion. The phosphorylation states of ERK1/2 and Akt by Western immunoblots were determined. Drugs were perfused for a period of 5 min before and 30 min after reperfusion.
Results:
Inhibition of ERK1/2 (26.8 ± 2.9%, P < 0.05 vs. U50) but not PI3K (15.5 ± 1.1%, P > 0.05 vs. U50) completely abrogated the anti-infarct effect of U50488H. Western blot analysis revealed a significant increase in ERK1/2 but not Akt phsophorylation in U50488H-treated hearts as compared to control hearts when measured immediately after reperfusion.
Conclusions:
KOP activation effectively reduces myocardial infarction. The anti-infarct effect of U50488H is mediated by the ERK1/2, but not the PI3K-Akt pathway.
Insights
κ-opioid receptor (KOP) activation protects against heart attack by activating ERK1/2. This study shows the extracellular signal-regulated kinases (ERK1/2) pathway, not PI3K-Akt, mediates this cardioprotective effect.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Molecular Biology
Background:
- Myocardial infarction remains a leading cause of mortality.
- κ-opioid receptor (KOP) activation has shown potential cardioprotective effects.
- The specific intracellular signaling pathways involved in KOP-mediated cardioprotection are not fully elucidated.
Purpose of the Study:
- To investigate the role of extracellular signal-regulated kinases (ERK1/2) and phosphatidylinositol-3-OH kinase (PI3K)-Akt pathways in KOP-mediated cardioprotection.
- To determine if KOP activation reduces myocardial infarct size through these signaling pathways.
Main Methods:
- Langendorff perfused rat hearts subjected to regional ischemia and reperfusion.
- Administration of KOP agonist U50488H with or without ERK1/2 and PI3K antagonists.
- Measurement of infarct size and Western blot analysis of ERK1/2 and Akt phosphorylation.
Main Results:
- KOP agonist U50488H significantly reduced infarct size.
- Inhibition of ERK1/2 completely abrogated the anti-infarct effect of U50488H.
- Inhibition of PI3K did not affect the cardioprotective action of U50488H, and only ERK1/2 phosphorylation was increased by U50488H.
Conclusions:
- KOP activation effectively reduces myocardial infarction.
- The cardioprotective effect of U50488H is mediated by the ERK1/2 pathway.
- The PI3K-Akt pathway is not involved in the anti-infarct effect of KOP activation in this model.
