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Role of Opioid Receptors Signaling in Remote Electrostimulation--Induced Protection against Ischemia/Reperfusion Injury in Rat Hearts.

Tsai HJ, Huang SS, Tsou MT, Wang HT, Chiu JH - PLoS ONE (2015)

Bottom Line: Our results showed that Akt, GSK3 and PKCε expression levels were significantly increased in the RES group compared to the sham group, which were blocked by pretreatment with specific antagonists targeting KOR and DOR, but not MOR subtype.Using the I/R model, the duration of arrhythmia and infarct size were both significantly attenuated in RES group.The mortality rates of the sham RES group, the RES group, RES group + KOR antagonist, RES group + DOR/MOR antagonists (KOR left), RES group + DOR antagonist, and RES group + KOR/MOR antagonists (DOR left) were 50%, 20%, 67%, 13%, 50% and 55%, respectively.

View Article: PubMed Central - PubMed

Affiliation: Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.

ABSTRACT

Aims: Our previous studies demonstrated that remote electro-stimulation (RES) increased myocardial GSK3 phosphorylation and attenuated ischemia/ reperfusion (I/R) injury in rat hearts. However, the role of various opioid receptors (OR) subtypes in preconditioned RES-induced myocardial protection remains unknown. We investigated the role of OR subtype signaling in RES-induced cardioprotection against I/R injury of the rat heart.

Methods & results: Male Spraque-Dawley rats were used. RES was performed on median nerves area with/without pretreatment with various receptors antagonists such as opioid receptor (OR) subtype receptors (KOR, DOR, and MOR). The expressions of Akt, GSK3, and PKCε expression were analyzed by Western blotting. When RES was preconditioned before the I/R model, the rat's hemodynamic index, infarction size, mortality and serum CK-MB were evaluated. Our results showed that Akt, GSK3 and PKCε expression levels were significantly increased in the RES group compared to the sham group, which were blocked by pretreatment with specific antagonists targeting KOR and DOR, but not MOR subtype. Using the I/R model, the duration of arrhythmia and infarct size were both significantly attenuated in RES group. The mortality rates of the sham RES group, the RES group, RES group + KOR antagonist, RES group + DOR/MOR antagonists (KOR left), RES group + DOR antagonist, and RES group + KOR/MOR antagonists (DOR left) were 50%, 20%, 67%, 13%, 50% and 55%, respectively.

Conclusion: The mechanism of RES-induced myocardial protection against I/R injury seems to involve multiple target pathways such as Akt, KOR and/or DOR signaling.

No MeSH data available.


Related in: MedlinePlus

The role of different opioid receptors subtype in hemodynamic changes of preconditioned remote electro-stimulation (RES)-induced myocardial protection against ischemia/reperfusion (I/R) injury.Animals were randomly allocated into 6 groups as described in Methods. They were 1) sham RES group (n = 24); 2) RES preconditioning group (n = 20); 3) RES preconditioning pretreated with KOR blocker (n = 18); 4) RES preconditioning pretreated with DOR blocker (n = 10); 5) RES preconditioning pretreated with KOR/MOR antagonists, which left DOR active (n = 11); 6) RES preconditioning pretreated with DOR/MOR antagonists, which left KOR active (n = 9). During I/R injury period, the hemodynamic changes in these animals were continuously monitored (A). The results showed that preconditioned RES seemed to maintain a higher mean arterial pressure (MAP) than the sham RES group (B). It was of note that there was a significant decreased MAP in preconditioned RES + KOR blocked group (C), but not in preconditioned RES + DOR blocked group (D), compared to the preconditioned RES group. *, p<0.05, vs. sham RES. KOR, kappa opioid receptor; DOR, delta opioid receptor; MOR, mu opioid receptor; KOR left, KOR activity remained; DOR left, DOR activity remained; MOR left, MOR activity remained.
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pone.0138108.g005: The role of different opioid receptors subtype in hemodynamic changes of preconditioned remote electro-stimulation (RES)-induced myocardial protection against ischemia/reperfusion (I/R) injury.Animals were randomly allocated into 6 groups as described in Methods. They were 1) sham RES group (n = 24); 2) RES preconditioning group (n = 20); 3) RES preconditioning pretreated with KOR blocker (n = 18); 4) RES preconditioning pretreated with DOR blocker (n = 10); 5) RES preconditioning pretreated with KOR/MOR antagonists, which left DOR active (n = 11); 6) RES preconditioning pretreated with DOR/MOR antagonists, which left KOR active (n = 9). During I/R injury period, the hemodynamic changes in these animals were continuously monitored (A). The results showed that preconditioned RES seemed to maintain a higher mean arterial pressure (MAP) than the sham RES group (B). It was of note that there was a significant decreased MAP in preconditioned RES + KOR blocked group (C), but not in preconditioned RES + DOR blocked group (D), compared to the preconditioned RES group. *, p<0.05, vs. sham RES. KOR, kappa opioid receptor; DOR, delta opioid receptor; MOR, mu opioid receptor; KOR left, KOR activity remained; DOR left, DOR activity remained; MOR left, MOR activity remained.

Mentions: During I/R injury period, the hemodynamic changes in these animals were continuously monitored (Fig 5A). The results showed that preconditioned RES seemed to maintain a higher mean blood pressure (MBP) than the sham RES group (Fig 5B). It was of note that there was a significant decreased MBP in preconditioned RES + KOR blocked group (Fig 5C), but not in preconditioned RES + DOR blocked group (Fig 5D), compared to the preconditioned RES group.


Role of Opioid Receptors Signaling in Remote Electrostimulation--Induced Protection against Ischemia/Reperfusion Injury in Rat Hearts.

Tsai HJ, Huang SS, Tsou MT, Wang HT, Chiu JH - PLoS ONE (2015)

The role of different opioid receptors subtype in hemodynamic changes of preconditioned remote electro-stimulation (RES)-induced myocardial protection against ischemia/reperfusion (I/R) injury.Animals were randomly allocated into 6 groups as described in Methods. They were 1) sham RES group (n = 24); 2) RES preconditioning group (n = 20); 3) RES preconditioning pretreated with KOR blocker (n = 18); 4) RES preconditioning pretreated with DOR blocker (n = 10); 5) RES preconditioning pretreated with KOR/MOR antagonists, which left DOR active (n = 11); 6) RES preconditioning pretreated with DOR/MOR antagonists, which left KOR active (n = 9). During I/R injury period, the hemodynamic changes in these animals were continuously monitored (A). The results showed that preconditioned RES seemed to maintain a higher mean arterial pressure (MAP) than the sham RES group (B). It was of note that there was a significant decreased MAP in preconditioned RES + KOR blocked group (C), but not in preconditioned RES + DOR blocked group (D), compared to the preconditioned RES group. *, p<0.05, vs. sham RES. KOR, kappa opioid receptor; DOR, delta opioid receptor; MOR, mu opioid receptor; KOR left, KOR activity remained; DOR left, DOR activity remained; MOR left, MOR activity remained.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4592126&req=5

pone.0138108.g005: The role of different opioid receptors subtype in hemodynamic changes of preconditioned remote electro-stimulation (RES)-induced myocardial protection against ischemia/reperfusion (I/R) injury.Animals were randomly allocated into 6 groups as described in Methods. They were 1) sham RES group (n = 24); 2) RES preconditioning group (n = 20); 3) RES preconditioning pretreated with KOR blocker (n = 18); 4) RES preconditioning pretreated with DOR blocker (n = 10); 5) RES preconditioning pretreated with KOR/MOR antagonists, which left DOR active (n = 11); 6) RES preconditioning pretreated with DOR/MOR antagonists, which left KOR active (n = 9). During I/R injury period, the hemodynamic changes in these animals were continuously monitored (A). The results showed that preconditioned RES seemed to maintain a higher mean arterial pressure (MAP) than the sham RES group (B). It was of note that there was a significant decreased MAP in preconditioned RES + KOR blocked group (C), but not in preconditioned RES + DOR blocked group (D), compared to the preconditioned RES group. *, p<0.05, vs. sham RES. KOR, kappa opioid receptor; DOR, delta opioid receptor; MOR, mu opioid receptor; KOR left, KOR activity remained; DOR left, DOR activity remained; MOR left, MOR activity remained.
Mentions: During I/R injury period, the hemodynamic changes in these animals were continuously monitored (Fig 5A). The results showed that preconditioned RES seemed to maintain a higher mean blood pressure (MBP) than the sham RES group (Fig 5B). It was of note that there was a significant decreased MBP in preconditioned RES + KOR blocked group (Fig 5C), but not in preconditioned RES + DOR blocked group (Fig 5D), compared to the preconditioned RES group.

Bottom Line: Our results showed that Akt, GSK3 and PKCε expression levels were significantly increased in the RES group compared to the sham group, which were blocked by pretreatment with specific antagonists targeting KOR and DOR, but not MOR subtype.Using the I/R model, the duration of arrhythmia and infarct size were both significantly attenuated in RES group.The mortality rates of the sham RES group, the RES group, RES group + KOR antagonist, RES group + DOR/MOR antagonists (KOR left), RES group + DOR antagonist, and RES group + KOR/MOR antagonists (DOR left) were 50%, 20%, 67%, 13%, 50% and 55%, respectively.

View Article: PubMed Central - PubMed

Affiliation: Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.

ABSTRACT

Aims: Our previous studies demonstrated that remote electro-stimulation (RES) increased myocardial GSK3 phosphorylation and attenuated ischemia/ reperfusion (I/R) injury in rat hearts. However, the role of various opioid receptors (OR) subtypes in preconditioned RES-induced myocardial protection remains unknown. We investigated the role of OR subtype signaling in RES-induced cardioprotection against I/R injury of the rat heart.

Methods & results: Male Spraque-Dawley rats were used. RES was performed on median nerves area with/without pretreatment with various receptors antagonists such as opioid receptor (OR) subtype receptors (KOR, DOR, and MOR). The expressions of Akt, GSK3, and PKCε expression were analyzed by Western blotting. When RES was preconditioned before the I/R model, the rat's hemodynamic index, infarction size, mortality and serum CK-MB were evaluated. Our results showed that Akt, GSK3 and PKCε expression levels were significantly increased in the RES group compared to the sham group, which were blocked by pretreatment with specific antagonists targeting KOR and DOR, but not MOR subtype. Using the I/R model, the duration of arrhythmia and infarct size were both significantly attenuated in RES group. The mortality rates of the sham RES group, the RES group, RES group + KOR antagonist, RES group + DOR/MOR antagonists (KOR left), RES group + DOR antagonist, and RES group + KOR/MOR antagonists (DOR left) were 50%, 20%, 67%, 13%, 50% and 55%, respectively.

Conclusion: The mechanism of RES-induced myocardial protection against I/R injury seems to involve multiple target pathways such as Akt, KOR and/or DOR signaling.

No MeSH data available.


Related in: MedlinePlus