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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 affecting infarction size in preconditioned remote electro-stimulation (RES)-induced myocardial protection against ischemia/reperfusion (I/R) injury.In the I/R model, 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). All of these groups received subsequent I/R injury, followed by evaluation of infarct size, such as grossly (A), area at risk (B) and infarcted size (C). Data are presented as mean ± S.E.M and were analyzed using repeated one-way analysis of variance (ANOVA) followed by the Dunnet’s test. A p value less than 0.05 is considered statistically significant. *, p<0.05, vs. sham RES; #, p<0.05, vs. 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.g004: The role of different opioid receptors subtype affecting infarction size in preconditioned remote electro-stimulation (RES)-induced myocardial protection against ischemia/reperfusion (I/R) injury.In the I/R model, 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). All of these groups received subsequent I/R injury, followed by evaluation of infarct size, such as grossly (A), area at risk (B) and infarcted size (C). Data are presented as mean ± S.E.M and were analyzed using repeated one-way analysis of variance (ANOVA) followed by the Dunnet’s test. A p value less than 0.05 is considered statistically significant. *, p<0.05, vs. sham RES; #, p<0.05, vs. 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: In the I/R model, animals were randomly allocated into 6 groups. 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). All of these groups received subsequent I/R injury, followed by evaluation of infarct size, such as grossly (Fig 4A) and relative weight (Fig 4B and 4C). The results showed that there was no significant difference, in terms of area at risk, between groups (Fig 4B). Preconditioned RES (23±3%) significantly decreased the infacted size compared to sham RES group (41±5%), which was blocked by pretreatment of KOR and DOR antagonists, either alone or in combination (Fig 4C). The infarct size after KOR was blocked, KOR was left active, DOR was blocked and DOR was left active were 81±2%, 39±4%, 55±5%, and 65±9%, respectively.


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 affecting infarction size in preconditioned remote electro-stimulation (RES)-induced myocardial protection against ischemia/reperfusion (I/R) injury.In the I/R model, 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). All of these groups received subsequent I/R injury, followed by evaluation of infarct size, such as grossly (A), area at risk (B) and infarcted size (C). Data are presented as mean ± S.E.M and were analyzed using repeated one-way analysis of variance (ANOVA) followed by the Dunnet’s test. A p value less than 0.05 is considered statistically significant. *, p<0.05, vs. sham RES; #, p<0.05, vs. 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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Show All Figures
getmorefigures.php?uid=PMC4592126&req=5

pone.0138108.g004: The role of different opioid receptors subtype affecting infarction size in preconditioned remote electro-stimulation (RES)-induced myocardial protection against ischemia/reperfusion (I/R) injury.In the I/R model, 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). All of these groups received subsequent I/R injury, followed by evaluation of infarct size, such as grossly (A), area at risk (B) and infarcted size (C). Data are presented as mean ± S.E.M and were analyzed using repeated one-way analysis of variance (ANOVA) followed by the Dunnet’s test. A p value less than 0.05 is considered statistically significant. *, p<0.05, vs. sham RES; #, p<0.05, vs. 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: In the I/R model, animals were randomly allocated into 6 groups. 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). All of these groups received subsequent I/R injury, followed by evaluation of infarct size, such as grossly (Fig 4A) and relative weight (Fig 4B and 4C). The results showed that there was no significant difference, in terms of area at risk, between groups (Fig 4B). Preconditioned RES (23±3%) significantly decreased the infacted size compared to sham RES group (41±5%), which was blocked by pretreatment of KOR and DOR antagonists, either alone or in combination (Fig 4C). The infarct size after KOR was blocked, KOR was left active, DOR was blocked and DOR was left active were 81±2%, 39±4%, 55±5%, and 65±9%, respectively.

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