Limits...
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

Study design and protocols.Two protocols were designed in this study, namely, 1) mechanistic study and 2) I/R model. In mechanistic protocol, various receptors antagonists were pretreated 15 min before remote electro-stimulation (RES). In I/R model, various receptors antagonists were pretreated 15 min before RES preconditioning, followed by 1h-ischemia and 3 h-reperfusion.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4592126&req=5

pone.0138108.g001: Study design and protocols.Two protocols were designed in this study, namely, 1) mechanistic study and 2) I/R model. In mechanistic protocol, various receptors antagonists were pretreated 15 min before remote electro-stimulation (RES). In I/R model, various receptors antagonists were pretreated 15 min before RES preconditioning, followed by 1h-ischemia and 3 h-reperfusion.

Mentions: Two protocols were designed in this study, namely, 1) mechanistic study and 2) I/R model. In mechanistic protocol, various receptors antagonists were pretreated 15 min before RES preconditioning. In the I/R model, animals were randomly allocated into 6 groups. They were 1) sham RES group; 2) RES preconditioning group; 3) RES preconditioning pretreated with KOR blocker; 4) RES preconditioning pretreated with DOR blocker; 5) RES preconditioning pretreated with KOR/MOR antagonists, which left DOR active; 6) RES preconditioning pretreated with DOR/MOR antagonists, which left KOR active. In this protocol, various receptors antagonists were pretreated 15 min before RES preconditioning, followed by ischemia for 1 h and reperfusion for 3 h (Fig 1). The combination of receptor antagonists and their corresponding abbreviations were shown in Table 1.


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)

Study design and protocols.Two protocols were designed in this study, namely, 1) mechanistic study and 2) I/R model. In mechanistic protocol, various receptors antagonists were pretreated 15 min before remote electro-stimulation (RES). In I/R model, various receptors antagonists were pretreated 15 min before RES preconditioning, followed by 1h-ischemia and 3 h-reperfusion.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4592126&req=5

pone.0138108.g001: Study design and protocols.Two protocols were designed in this study, namely, 1) mechanistic study and 2) I/R model. In mechanistic protocol, various receptors antagonists were pretreated 15 min before remote electro-stimulation (RES). In I/R model, various receptors antagonists were pretreated 15 min before RES preconditioning, followed by 1h-ischemia and 3 h-reperfusion.
Mentions: Two protocols were designed in this study, namely, 1) mechanistic study and 2) I/R model. In mechanistic protocol, various receptors antagonists were pretreated 15 min before RES preconditioning. In the I/R model, animals were randomly allocated into 6 groups. They were 1) sham RES group; 2) RES preconditioning group; 3) RES preconditioning pretreated with KOR blocker; 4) RES preconditioning pretreated with DOR blocker; 5) RES preconditioning pretreated with KOR/MOR antagonists, which left DOR active; 6) RES preconditioning pretreated with DOR/MOR antagonists, which left KOR active. In this protocol, various receptors antagonists were pretreated 15 min before RES preconditioning, followed by ischemia for 1 h and reperfusion for 3 h (Fig 1). The combination of receptor antagonists and their corresponding abbreviations were shown in Table 1.

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