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<p>Chronic continuous hypoxia (CCH) demonstrates a pronounced protective effect in cardiac ischemia-reperfusion (IR). Opioids and opioid receptors play a significant role in this process. It has been previously shown that metabolic syndrome (MS) impairs the development of adaptive myocardial resistance to IR. The aim of this study is to identify the relationship between the cardioprotective effect of CCH and opioid peptides in circulating blood and myocardial tissue, as well as the expression of opioid receptors in the myocardium of rats with and without MS.&#xa0;All rats were subjected to coronary artery occlusion (45&#xa0;min) and reperfusion (2&#xa0;h). Some rats received high carbohydrate high fat diet for 90 days (MS) before IR. Some animals were exposed to CCH (21 days, 12% O<sub>2</sub>) before IR.&#xa0;The plasma endomorphin-2, and dynorphin A levels were increased after CCH. Endomorphin-2, β-endorphin, dynorphin A (1–13), and met-enkephalin content in myocardial tissue was increased in response to CCH. In rats with MS, an increase in the plasma and myocardial opioid levels in response to CCH was reduced. A correlation was identified between plasma and myocardial tissue opioid peptide levels and the extent of myocardial injury, as well as between myocardial opioid peptide content and contractility. Furthermore, CCH and MS caused a reduction in the expression of δ- (DOR) and κ- (KOR) opioid receptors, and also an increase in µ- (MOR) opioid receptor expression.&#xa0;These findings suggest that a decrease in opioid peptide content could impair adaptive cardioprotection in MS.</p> Graphical abstract <p></p>

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Metabolic syndrome reduces but does not eliminate the cardioprotective effect of adaptation to hypoxia: the link with changes in the opioid system

  • 期刊论文

  • 发表日期：

    2025年12月8日

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  • Natalia V. Naryzhnaya,
  • Ivan A. Derkachev,
  • Boris K. Kurbatov,
  • Alexander V. Mukhomedzyanov,
  • Mikhail Kilin,
  • Artur Kan,
  • Alexandr E. Grab,
  • Alla A. Boschenko,
  • Leonid N. Maslov

摘要

Chronic continuous hypoxia (CCH) demonstrates a pronounced protective effect in cardiac ischemia-reperfusion (IR). Opioids and opioid receptors play a significant role in this process. It has been previously shown that metabolic syndrome (MS) impairs the development of adaptive myocardial resistance to IR. The aim of this study is to identify the relationship between the cardioprotective effect of CCH and opioid peptides in circulating blood and myocardial tissue, as well as the expression of opioid receptors in the myocardium of rats with and without MS. All rats were subjected to coronary artery occlusion (45 min) and reperfusion (2 h). Some rats received high carbohydrate high fat diet for 90 days (MS) before IR. Some animals were exposed to CCH (21 days, 12% O2) before IR. The plasma endomorphin-2, and dynorphin A levels were increased after CCH. Endomorphin-2, β-endorphin, dynorphin A (1–13), and met-enkephalin content in myocardial tissue was increased in response to CCH. In rats with MS, an increase in the plasma and myocardial opioid levels in response to CCH was reduced. A correlation was identified between plasma and myocardial tissue opioid peptide levels and the extent of myocardial injury, as well as between myocardial opioid peptide content and contractility. Furthermore, CCH and MS caused a reduction in the expression of δ- (DOR) and κ- (KOR) opioid receptors, and also an increase in µ- (MOR) opioid receptor expression. These findings suggest that a decrease in opioid peptide content could impair adaptive cardioprotection in MS.

Graphical abstract