open access

Vol 24, No 3 (2017)
Original articles — Basic science and experimental cardiology
Published online: 2016-09-01
Get Citation

Activating mu-opioid receptors in the spinal cord mediates the cardioprotective effect of remote preconditioning of trauma

Bin Mei, Wanhong Li, Xinqi Cheng, Xuesheng Liu, Erwei Gu, Ye Zhang
DOI: 10.5603/CJ.a2016.0062
·
Pubmed: 27586455
·
Cardiol J 2017;24(3):314-323.

open access

Vol 24, No 3 (2017)
Original articles — Basic science and experimental cardiology
Published online: 2016-09-01

Abstract

Background: Remote precoditioning of trauma (RPCT) confers cardioprotective effects against myocardial ischemia/reperfusion injury, which are mediated by spinal opioid receptors. The aim of this study was to identify the roles of opioid receptor subtypes in the cardioprotective effect of RPCT and possible mechanisms.

Methods: In this study, 192 Sprague-Dawley rats were allocated to 12 groups. Except for the sham group, rats in all groups were subjected to myocardial ischemia reperfusion. Rats in the ischemia precondition (IPC) group were treated with IPC. In the RPCT groups, an abdominal incision was made 15 min before inducing ischemia. The selective delta-, kappa-, and mu-opioid receptor antagonists were administered to groups of animals receiving RPCT, respectively. Data were collected for myocardial infarct size, intercellular adhesion molecule 1 (ICAM-1), plasma cardiac troponin I (cTnI) concentrations, activation of protein kinase C epsilon (PKCe) in myocardial cell membranes, and adenosine release in the spinal cord.

Results: Compared with the control groups, infarct size, plasma concentrations of cTnI, and myocardial ICAM-1 expression were significantly lower, while adenosine release and PKCe activation were enhanced in the IPC and RPCT groups. Compared with the RPCT group, infarct size, plasma cTnI concentration, and myocardial ICAM-1 expression were greater and adenosine release and PKCe activation were reduced in the mu-opioid receptor antagonist plus RPCT group.

Conclusions: The spinal mu-opioid receptor mediated the cardiac protective effect of RPCT. The mechanism may be enhanced by adenosine release in the spinal cord and PKCe activation in the myo­cardium, thereby inhibiting inflammation induced by ischemia/reperfusion injury.

Abstract

Background: Remote precoditioning of trauma (RPCT) confers cardioprotective effects against myocardial ischemia/reperfusion injury, which are mediated by spinal opioid receptors. The aim of this study was to identify the roles of opioid receptor subtypes in the cardioprotective effect of RPCT and possible mechanisms.

Methods: In this study, 192 Sprague-Dawley rats were allocated to 12 groups. Except for the sham group, rats in all groups were subjected to myocardial ischemia reperfusion. Rats in the ischemia precondition (IPC) group were treated with IPC. In the RPCT groups, an abdominal incision was made 15 min before inducing ischemia. The selective delta-, kappa-, and mu-opioid receptor antagonists were administered to groups of animals receiving RPCT, respectively. Data were collected for myocardial infarct size, intercellular adhesion molecule 1 (ICAM-1), plasma cardiac troponin I (cTnI) concentrations, activation of protein kinase C epsilon (PKCe) in myocardial cell membranes, and adenosine release in the spinal cord.

Results: Compared with the control groups, infarct size, plasma concentrations of cTnI, and myocardial ICAM-1 expression were significantly lower, while adenosine release and PKCe activation were enhanced in the IPC and RPCT groups. Compared with the RPCT group, infarct size, plasma cTnI concentration, and myocardial ICAM-1 expression were greater and adenosine release and PKCe activation were reduced in the mu-opioid receptor antagonist plus RPCT group.

Conclusions: The spinal mu-opioid receptor mediated the cardiac protective effect of RPCT. The mechanism may be enhanced by adenosine release in the spinal cord and PKCe activation in the myo­cardium, thereby inhibiting inflammation induced by ischemia/reperfusion injury.

Get Citation

Keywords

opioid receptor, remote preconditioning of trauma, myocardial reperfusion injury, spinal cord, adenosine, inflammation

About this article
Title

Activating mu-opioid receptors in the spinal cord mediates the cardioprotective effect of remote preconditioning of trauma

Journal

Cardiology Journal

Issue

Vol 24, No 3 (2017)

Pages

314-323

Published online

2016-09-01

DOI

10.5603/CJ.a2016.0062

Pubmed

27586455

Bibliographic record

Cardiol J 2017;24(3):314-323.

Keywords

opioid receptor
remote preconditioning of trauma
myocardial reperfusion injury
spinal cord
adenosine
inflammation

Authors

Bin Mei
Wanhong Li
Xinqi Cheng
Xuesheng Liu
Erwei Gu
Ye Zhang

References (30)
  1. Ren X, Wang Y, Jones WK. TNF-alpha is required for late ischemic preconditioning but not for remote preconditioning of trauma. J Surg Res. 2004; 121(1): 120–129.
  2. Jones WK, Fan GC, Liao S, et al. Peripheral nociception associated with surgical incision elicits remote nonischemic cardioprotection via neurogenic activation of protein kinase C signaling. Circulation. 2009; 120(11 Suppl): S1–S9.
  3. Wong GT, Lu Y, Mei B, et al. Cardioprotection from remote preconditioning involves spinal opioid receptor activation. Life Sci. 2012; 91(17-18): 860–865.
  4. Gross GJ, Hsu A, Gross ER, et al. Factors mediating remote preconditioning of trauma in the rat heart: central role of the cytochrome p450 epoxygenase pathway in mediating infarct size reduction. J Cardiovasc Pharmacol Ther. 2013; 18(1): 38–45.
  5. Headrick JP, See Hoe LE, Du Toit EF, et al. Opioid receptors and cardioprotection - 'opioidergic conditioning' of the heart. Br J Pharmacol. 2015; 172(8): 2026–2050.
  6. Li R, Wong GTC, Wong TM, et al. Intrathecal morphine preconditioning induces cardioprotection via activation of delta, kappa, and mu opioid receptors in rats. Anesth Analg. 2009; 108(1): 23–29.
  7. Sandner-Kiesling A, Li X, Eisenach JC. Morphine-induced spinal release of adenosine is reduced in neuropathic rats. Anesthesiology. 2001; 95(6): 1455–1459.
  8. Eisenach JC, Hood DD, Curry R, et al. Intrathecal but not intravenous opioids release adenosine from the spinal cord. J Pain. 2004; 5(1): 64–68.
  9. Bong GW, Rosengren S, Firestein GS. Spinal cord adenosine receptor stimulation in rats inhibits peripheral neutrophil accumulation. The role of N-methyl-D-aspartate receptors. J Clin Invest. 1996; 98(12): 2779–2785.
  10. Yaksh T, Rudy T. Chronic catheterization of the spinal subarachnoid space. Physiology Behavior. 1976; 17(6): 1031–1036.
  11. Zhang Ye, Irwin MG, Lu Y, et al. Intracerebroventricular administration of morphine confers remote cardioprotection--role of opioid receptors and calmodulin. Eur J Pharmacol. 2011; 656(1-3): 74–80.
  12. Chen QL, Gu EW, Zhang L, et al. Diabetes mellitus abrogates the cardioprotection of sufentanil against ischaemia/reperfusion injury by altering glycogen synthase kinase-3β. Acta Anaesthesiol Scand. 2013; 57(2): 236–242.
  13. Bilgir F, Bilgir O, Calan M, et al. The levels of adhesion molecules in essential thrombocythemia. Panminerva Med. 2013; 55(4): 385–390.
  14. Hagberg H, Andersson P, Lacarewicz J, et al. Extracellular adenosine, inosine, hypoxanthine, and xanthine in relation to tissue nucleotides and purines in rat striatum during transient ischemia. J Neurochem. 1987; 49(1): 227–231.
  15. Song Y, Ye YJ, Li PW, et al. The Cardioprotective Effects of Late-Phase Remote Preconditioning of Trauma Depends on Neurogenic Pathways and the Activation of PKC and NF-κB (But Not iNOS) in Mice. J Cardiovasc Pharmacol Ther. 2016; 21(3): 310–319.
  16. Chai Q, Liu J, Hu Y. Cardioprotective effect of remote preconditioning of trauma and remote ischemia preconditioning in a rat model of myocardial ischemia/reperfusion injury. Exp Ther Med. 2015; 9(5): 1745–1750.
  17. Ruiz-Meana M, Martinson EA, Garcia-Dorado D, et al. Animal ethics in cardiovascular research. Cardiovasc Res. 2012; 93(1): 1–3.
  18. Wrigley PJ, Jeong HJ, Vaughan CW. Dissociation of μ- and δ-opioid inhibition of glutamatergic synaptic transmission in superficial dorsal horn. Mol Pain. 2010; 6: 71.
  19. Chen SR, Pan HL. Blocking mu opioid receptors in the spinal cord prevents the analgesic action by subsequent systemic opioids. Brain Res. 2006; 1081(1): 119–125.
  20. DeLander GE, Hopkins CJ. Spinal adenosine modulates descending antinociceptive pathways stimulated by morphine. J Pharmacol Exp Ther. 1986; 239(1): 88–93.
  21. Sawynok J, Liu XJ. Adenosine in the spinal cord and periphery: release and regulation of pain. Prog Neurobiol. 2003; 69(5): 313–340.
  22. Boyle DL, Moore J, Yang Li, et al. Spinal adenosine receptor activation inhibits inflammation and joint destruction in rat adjuvant-induced arthritis. Arthritis Rheum. 2002; 46(11): 3076–3082.
  23. Carlsen EM, Perrier JF. Purines released from astrocytes inhibit excitatory synaptic transmission in the ventral horn of the spinal cord. Front Neural Circuits. 2014; 8: 60.
  24. Corradetti R, Lo Conte G, Moroni F, et al. Adenosine decreases aspartate and glutamate release from rat hippocampal slices. Eur J Pharmacol. 1984; 104(1-2): 19–26.
  25. Schaible HG, Grubb BD, Neugebauer V, et al. The Effects of NMDA Antagonists on Neuronal Activity in Cat Spinal Cord Evoked by Acute Inflammation in the Knee Joint. Eur J Neurosci. 1991; 3(10): 981–991.
  26. Neugebauer V, Lücke T, Schaible HG. N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists block the hyperexcitability of dorsal horn neurons during development of acute arthritis in rat's knee joint. J Neurophysiol. 1993; 70(4): 1365–1377.
  27. Sluka KA, Westlund KN. An experimental arthritis in rats: dorsal horn aspartate and glutamate increases. Neurosci Lett. 1992; 145(2): 141–144.
  28. Wei W, Wei FC, Hung LM. Diazoxide ameliorates microcirculatory disturbances through PKC-dependent pathway in I/R-injured rat cremaster muscles. J Biomed Sci. 2005; 12(3): 521–529.
  29. Teng JCw, Kay H, Chen Q, et al. Mechanisms related to the cardioprotective effects of protein kinase C epsilon (PKC epsilon) peptide activator or inhibitor in rat ischemia/reperfusion injury. Naunyn Schmiedebergs Arch Pharmacol. 2008; 378(1): 1–15.
  30. Yao Lu, Wong GT, Xia Z, et al. Interaction between spinal opioid and adenosine receptors in remote cardiac preconditioning: effect of intrathecal morphine. J Cardiothorac Vasc Anesth. 2011; 25(3): 444–448.

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk, Poland
tel.:+48 58 320 94 94, fax:+48 58 320 94 60, e-mail: viamedica@viamedica.pl