Delta Opioid Receptors and Cardioprotection

Hoe, Louise E. See; Patel, Hemal H.; Peart, Jason Nigel John

doi:10.1007/164_2017_6

Cited by 14 publications

(4 citation statements)

References 289 publications

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“…Due to their presumed neutral hemodynamic effects, high-dose opioids are widely used to provide analgesia in high-risk patients undergoing anesthesia [ 28 , 29 ]. Opioids also seem to protect the heart from ischemia/reperfusion (IR) injury, and are, thus, a cornerstone of cardiac and high-risk non-cardiac anesthesia [ 30 ]. Interestingly, especially amongst elderly patients (age > 75 years) and patients with concomitant congestive heart failure (CHF); intravenous morphine increased in-hospital mortality when administered in acute coronary syndromes [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Chronic Naltrexone Therapy Is Associated with Improved Cardiac Function in Volume Overloaded Rats

Dehe

Shaqura

Nordine

et al. 2021

Cardiovasc Drugs Ther

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Purpose Myocardial opioid receptors were demonstrated in animals and humans and seem to colocalize with membranous and sarcolemmal calcium channels of the excitation–contraction coupling in the left ventricle (LV). Therefore, this study investigated whether blockade of the cardiac opioid system by naltrexone would affect cardiac function and neurohumoral parameters in Wistar rats with volume overload-induced heart failure. Methods Volume overload in Wistar rats was induced by an aortocaval fistula (ACF). Left ventricular cardiac opioid receptors were identified by immunohistochemistry and their messenger ribonucleic acid (mRNA) as well as their endogenous ligand mRNA quantified by real-time polymerase chain reaction (RT-PCR). Following continuous delivery of either the opioid receptor antagonist naltrexone or vehicle via minipumps (n = 5 rats each), hemodynamic and humoral parameters were assessed 28 days after ACF induction. Sham-operated animals served as controls. Results In ACF rats mu-, delta-, and kappa-opioid receptors colocalized with voltage-gated L-type Ca2+ channels in left ventricular cardiomyocytes. Chronic naltrexone treatment of ACF rats reduced central venous pressure (CVP) and left ventricular end-diastolic pressure (LVEDP), and improved systolic and diastolic left ventricular functions. Concomitantly, rat brain natriuretic peptide (rBNP-45) and angiotensin-2 plasma concentrations which were elevated during ACF were significantly diminished following naltrexone treatment. In parallel, chronic naltrexone significantly reduced mu-, delta-, and kappa-opioid receptor mRNA, while it increased the endogenous opioid peptide mRNA compared to controls. Conclusion Opioid receptor blockade by naltrexone leads to improved LV function and decreases in rBNP-45 and angiotensin-2 plasma levels. In parallel, naltrexone resulted in opioid receptor mRNA downregulation and an elevated intrinsic tone of endogenous opioid peptides possibly reflecting a potentially cardiodepressant effect of the cardiac opioid system during volume overload.

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Section: Discussionmentioning

confidence: 99%

Chronic Naltrexone Therapy Is Associated with Improved Cardiac Function in Volume Overloaded Rats

Dehe

Shaqura

Nordine

et al. 2021

Cardiovasc Drugs Ther

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“… 61 Glycine receptor was found to exert a protective effect in myocardial cells, 62 whereas δ-opioid receptors not only influence systemic vascular tone but also impact cardiovascular autonomic balance. 63 Finally, cardiac μ-opioid receptors were proposed as a potential target in the treatment of myocardial ischemia-reperfusion injury during doxorubicin-induced chronic heart failure. 64 Despite the great potential of described receptors in targeting CVDs, their interaction with CBD is not yet fully recognized and needs further investigation.…”

Section: Pcbsmentioning

confidence: 99%

How do phytocannabinoids affect cardiovascular health? An update on the most common cardiovascular diseases

Dziemitko

Harasim-Symbor

Chabowski

2023

Therapeutic Advances in Chronic Disease

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Cardiovascular disease (CVD) causes millions of deaths worldwide each year. Despite the great progress in therapies available for patients with CVD, some limitations, including drug complications, still exist. Hence, the endocannabinoid system (ECS) was proposed as a new avenue for CVDs treatment. The ECS components are widely distributed through the body, including the heart and blood vessels, thus the action of its endogenous and exogenous ligands, in particular, phytocannabinoids play a key role in various pathological states. The cardiovascular action of cannabinoids is complex as they affect vasculature and myocardium directly via specific receptors and exert indirect effects through the central and peripheral nervous system. The growing interest in phytocannabinoid studies, however, has extended the knowledge about their molecular targets as well as therapeutical properties; nonetheless, some areas of their actions are not yet fully recognized. Researchers have reported various cannabinoids, especially cannabidiol, as a promising approach to CVDs; hence, the purpose of this review is to summarize and update the cardiovascular actions of the most potent phytocannabinoids and the potential therapeutic role of ECS in CVDs, including ischemic reperfusion injury, arrhythmia, heart failure as well as hypertension.

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“…Myocardial ischemia/reperfusion (I/R) injury can be extremely severe or even fatal, reducing remarkably the benefits of revascularization in acute myocardial infarction. Increasing evidence shows that opioid receptors are an emerging therapeutic target in I/R injury and cardioprotection [ 1 , 2 ]. Recent clinical trials using opioid receptor agonists during coronary artery bypass surgery have yielded encouraging results in reducing myocardial injury [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

New targets of morphine postconditioning protection of the myocardium in ischemia/reperfusion injury: Involvement of HSP90/Akt and C5a/NF-κB

Wang

Zhong

et al. 2021

Open Medicine

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Background Activation of the complement component 5a (C5a) and nuclear factor κB (NF-κB) signaling is an important feature of myocardial ischemia/reperfusion (I/R) injury and recent studies show that morphine postconditioning (MP) attenuates the myocardial injury. However, the mediating cardioprotective mechanisms remain unclear. The present study explores the role and interaction of heat shock protein 90 (HSP90), Akt, C5a, and NF-κB in MP-induced cardioprotection. Methods Male Sprague Dawley rats (n = 160) were randomized into eight groups (n = 20 per group). Rats in the sham group underwent thoracotomy, passing the ligature through the heart but without tying it (150 min), and the other seven groups were subjected to 30 min of anterior descending coronary artery occlusion followed by 2 h of reperfusion and the following treatments: I/R (30 min of ischemia and followed by 2 h of reperfusion); ischemic postconditioning (IPostC, 30 s of ischemia altered with 30 s of reperfusion, repeated for three cycles, and followed by reperfusion for 2 h); MP (0.3 mg/kg morphine administration 10 min before reperfusion); MP combined with the HSP90 inhibitor geldanamycin (GA, 1 mg/kg); MP combined with the Akt inhibitor GSK-690693 (GSK, 20 mg/kg); and MP combined with the C5a inhibitor PMX205 (PMX, 1 mg/kg/day, administration via drinking water for 28 days) and MP combined with the NF-κB inhibitor EVP4593 (QNZ, 1 mg/kg). All inhibitors were administered 10 min before morphine and followed by 2 h reperfusion. Results MP significantly reduced the I/R-induced infarct size, the apoptosis, and the release of cardiac troponin I, lactate dehydrogenase (LDH), and creatine kinase-MB. These beneficial effects were accompanied by increased expression of HSP90 and p-Akt, and decreased expression of C5a, NF-κB, tumor necrosis factor α, interleukin-1β, and intercellular cell adhesion molecule 1. However, HSP90 inhibitor GA or Akt inhibitor GSK increased the expression of C5a and NF-κB and prevented MP-induced cardioprotection. Furthermore, GA inhibited the MP-induced upregulation of p-Akt, while GSK did not affect HSP90, indicating that p-Akt acts downstream of HSP90 in MP-induced cardioprotection. In addition, C5a inhibitor PMX enhanced the MP-induced downregulation of NF-κB, while NF-κB inhibitor QNZ had no effect on C5a, indicating that the C5a/NF-κB signaling pathway is involved in MP-induced cardioprotection. Conclusion HSP90 is critical for MP-mediated cardioprotection possibly by promoting the phosphorylation of Akt and inhibiting the activation of C5a and NF-κB signaling and the subsequent myocardial inflammation, ultimately attenuating the infarct size and cardiomyocyte apoptosis.

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Delta Opioid Receptors and Cardioprotection

Cited by 14 publications

References 289 publications

Chronic Naltrexone Therapy Is Associated with Improved Cardiac Function in Volume Overloaded Rats

Chronic Naltrexone Therapy Is Associated with Improved Cardiac Function in Volume Overloaded Rats

How do phytocannabinoids affect cardiovascular health? An update on the most common cardiovascular diseases

New targets of morphine postconditioning protection of the myocardium in ischemia/reperfusion injury: Involvement of HSP90/Akt and C5a/NF-κB

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