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Role of Endogenous Opioid System in Ischemic-Induced Late Preconditioning.

Fraessdorf J, Hollmann MW, Hanschmann I, Heinen A, Weber NC, Preckel B, Huhn R - PLoS ONE (2015)

Bottom Line: We investigated whether 1) OR are involved in the trigger and/or mediation phase of LPC and 2) a time course effect on the expression of different opioid receptors and their endogenous ligands exists.LPC reduced infarct size from 61±10% in controls to 25±9% (P<0.001).Expression of δ-OR and plasma levels of endogenous opioid peptides are increased after ischemic LPC.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, University Hospital Duesseldorf, Duesseldorf, Germany; Department of Anesthesiology, Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands.

ABSTRACT

Background: Opioid receptors (OR) are involved in myocardial late preconditioning (LPC) induced by morphine and δ1-opioid receptor (δ1-OR) agonists. The role of OR in ischemic-induced LPC is unknown. We investigated whether 1) OR are involved in the trigger and/or mediation phase of LPC and 2) a time course effect on the expression of different opioid receptors and their endogenous ligands exists.

Methods: Male Wistar rats were randomly allocated to four groups (each group n = 8). Awake animals were ischemic preconditioned by a 5 minutes coronary occlusion. 24 hours later, anesthetized animals underwent 25 minutes coronary occlusion followed by 2 hours of reperfusion. The role of OR was investigated by treatment with intraperitoneal naloxone (Nal) 10 minutes prior to LPC (Nal-LPC; trigger phase) or 10 min prior to sustained ischemia (LPC-Nal; mediation phase).

Results: LPC reduced infarct size from 61±10% in controls to 25±9% (P<0.001). Naloxone during trigger or mediation phase completely abolished LPC-induced cardioprotection (59±9% and 62±9%; P<0.001 vs. LPC). 8, 12 and 24 hours after the ischemic stimulus, expression of δ-OR in the heart was increased, whereas μ-opioid receptor (μ-OR) and κ-opioid receptor (κ-OR) were not. Plasma concentrations of β-endorphin and leu-enkephalin but not dynorphin were increased by LPC.

Conclusion: Ischemic LPC is triggererd and mediated by OR. Expression of δ-OR and plasma levels of endogenous opioid peptides are increased after ischemic LPC.

No MeSH data available.


Related in: MedlinePlus

Plasma concentrations (ng/ml) of the endogenous opioids β-endorphin, dynorphin and leu-enkephalin in rat myocardium upon ischemic LPC (Sham, 0, 2, 4, 8, 12 and 24 hours after the ischemic stimulus was initiated).Data are presented as mean±SD, *P<0.05 vs. 0 hours.
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pone.0134283.g004: Plasma concentrations (ng/ml) of the endogenous opioids β-endorphin, dynorphin and leu-enkephalin in rat myocardium upon ischemic LPC (Sham, 0, 2, 4, 8, 12 and 24 hours after the ischemic stimulus was initiated).Data are presented as mean±SD, *P<0.05 vs. 0 hours.

Mentions: 12 and 24 hours after the preconditioning stimulus, plasma concentrations of β-endorphin were increased (12h: 0.65±0.16 ng/ml, 24h: 0.69±0.22 ng/ml; each P<0.01 vs. Con: 0.23±0.08 ng/ml, Fig 4). Plasma concentrations of leu-enkephalin were elevated 4, 8 and 24 hours after ischemic LPC (4h: 1.00±0.04 ng/ml, 8h: 1.01±0.03 ng/ml, 24h: 0.97±0.02 ng/ml; each P<0.01 vs. Con: 0.60±0.05 ng/ml, Fig 4). There were no changes in dynorphin plasma concentrations at all measured time points (Fig 4).


Role of Endogenous Opioid System in Ischemic-Induced Late Preconditioning.

Fraessdorf J, Hollmann MW, Hanschmann I, Heinen A, Weber NC, Preckel B, Huhn R - PLoS ONE (2015)

Plasma concentrations (ng/ml) of the endogenous opioids β-endorphin, dynorphin and leu-enkephalin in rat myocardium upon ischemic LPC (Sham, 0, 2, 4, 8, 12 and 24 hours after the ischemic stimulus was initiated).Data are presented as mean±SD, *P<0.05 vs. 0 hours.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4520665&req=5

pone.0134283.g004: Plasma concentrations (ng/ml) of the endogenous opioids β-endorphin, dynorphin and leu-enkephalin in rat myocardium upon ischemic LPC (Sham, 0, 2, 4, 8, 12 and 24 hours after the ischemic stimulus was initiated).Data are presented as mean±SD, *P<0.05 vs. 0 hours.
Mentions: 12 and 24 hours after the preconditioning stimulus, plasma concentrations of β-endorphin were increased (12h: 0.65±0.16 ng/ml, 24h: 0.69±0.22 ng/ml; each P<0.01 vs. Con: 0.23±0.08 ng/ml, Fig 4). Plasma concentrations of leu-enkephalin were elevated 4, 8 and 24 hours after ischemic LPC (4h: 1.00±0.04 ng/ml, 8h: 1.01±0.03 ng/ml, 24h: 0.97±0.02 ng/ml; each P<0.01 vs. Con: 0.60±0.05 ng/ml, Fig 4). There were no changes in dynorphin plasma concentrations at all measured time points (Fig 4).

Bottom Line: We investigated whether 1) OR are involved in the trigger and/or mediation phase of LPC and 2) a time course effect on the expression of different opioid receptors and their endogenous ligands exists.LPC reduced infarct size from 61±10% in controls to 25±9% (P<0.001).Expression of δ-OR and plasma levels of endogenous opioid peptides are increased after ischemic LPC.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, University Hospital Duesseldorf, Duesseldorf, Germany; Department of Anesthesiology, Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands.

ABSTRACT

Background: Opioid receptors (OR) are involved in myocardial late preconditioning (LPC) induced by morphine and δ1-opioid receptor (δ1-OR) agonists. The role of OR in ischemic-induced LPC is unknown. We investigated whether 1) OR are involved in the trigger and/or mediation phase of LPC and 2) a time course effect on the expression of different opioid receptors and their endogenous ligands exists.

Methods: Male Wistar rats were randomly allocated to four groups (each group n = 8). Awake animals were ischemic preconditioned by a 5 minutes coronary occlusion. 24 hours later, anesthetized animals underwent 25 minutes coronary occlusion followed by 2 hours of reperfusion. The role of OR was investigated by treatment with intraperitoneal naloxone (Nal) 10 minutes prior to LPC (Nal-LPC; trigger phase) or 10 min prior to sustained ischemia (LPC-Nal; mediation phase).

Results: LPC reduced infarct size from 61±10% in controls to 25±9% (P<0.001). Naloxone during trigger or mediation phase completely abolished LPC-induced cardioprotection (59±9% and 62±9%; P<0.001 vs. LPC). 8, 12 and 24 hours after the ischemic stimulus, expression of δ-OR in the heart was increased, whereas μ-opioid receptor (μ-OR) and κ-opioid receptor (κ-OR) were not. Plasma concentrations of β-endorphin and leu-enkephalin but not dynorphin were increased by LPC.

Conclusion: Ischemic LPC is triggererd and mediated by OR. Expression of δ-OR and plasma levels of endogenous opioid peptides are increased after ischemic LPC.

No MeSH data available.


Related in: MedlinePlus