Cannabinoid/agonist WIN 55,212‐2 reduces cardiac ischaemia–reperfusion injury in Zucker diabetic fatty rats: role of CB2 receptors and iNOS/eNOS

González, Cristina; Herradón, Esperanza; Abalo, Raquel; Vera, Gema; Perez‐Nievas, Beatriz Gomez; Leza, Juan C.; Martín, M. I. Fernández San; López‐Miranda, Visitación

doi:10.1002/dmrr.1176

Cited by 44 publications

(36 citation statements)

References 66 publications

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“…Cause and effect is difficult to determine in this type of experiment, however, the fact that WIN 55,212-2 is protective in neutrophil-free isolated hearts would argue for the second hypothesis. 43 The above data are strongly supported by the results of Wang et al 5 who also used mice. Hearts were subjected to either 30 min coronary artery occlusion and 24 h reperfusion or 24 h of continuous occlusion.…”

Section: Controversy As To Which Cannabinoid Receptors Protect the Heartsupporting

confidence: 65%

“…The reduction of coronary resistance was interpreted by the authors as a vasoprotective effect. 43 The vasoprotective effect was unaffected by the blockade of CB1 receptors but disappeared after inhibition of CB2 receptors. 43 They concluded that exogenous cannabinoids prevent injury to the endothelium of coronary arteries evoked by ischemia/reperfusion via activation of CB2 receptors.…”

Section: Cannabinoids and The No-reflow Phenomenonmentioning

confidence: 99%

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Prospects for Creation of Cardioprotective Drugs Based on Cannabinoid Receptor Agonists

Maslov

Khaliulin

Zhang

et al. 2015

J Cardiovasc Pharmacol Ther

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Cannabinoids can mimic the infarct-reducing effect of early ischemic preconditioning, delayed ischemic preconditioning, and ischemic postconditioning against myocardial ischemia/reperfusion. They do this primarily through both CB1 and CB2 receptors. Cannabinoids are also involved in remote preconditioning of the heart. The cannabinoid receptor ligands also exhibit an antiapoptotic effect during ischemia/reperfusion of the heart. The acute cardioprotective effect of cannabinoids is mediated by activation of protein kinase C, extracellular signal-regulated kinase, and p38 kinase. The delayed cardioprotective effect of cannabinoid anandamide is mediated via stimulation of phosphatidylinositol-3-kinase-Akt signaling pathway and enhancement of heat shock protein 72 expression. The delayed cardioprotective effect of another cannabinoid, D9-tetrahydrocannabinol, is associated with augmentation of nitric oxide (NO) synthase expression, but data on the involvement of NO synthase in the acute cardioprotective effect of cannabinoids are contradictory. The adenosine triphosphate-sensitive K þ channel is involved in the synthetic cannabinoid HU-210-induced cardiac resistance to ischemia/reperfusion injury. Cannabinoids inhibit Na þ /Ca 2þ exchange via peripheral cannabinoid receptor (CB2) activation that may also be related to the antiapoptotic and cardioprotective effects of cannabinoids. The cannabinoid receptor agonists should be considered as prospective group of compounds for creation of drugs that are able to protect the heart against ischemia-reperfusion injury in the clinical setting.

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Section: Controversy As To Which Cannabinoid Receptors Protect the Heartsupporting

confidence: 65%

Section: Cannabinoids and The No-reflow Phenomenonmentioning

confidence: 99%

Prospects for Creation of Cardioprotective Drugs Based on Cannabinoid Receptor Agonists

Maslov

Khaliulin

Zhang

et al. 2015

J Cardiovasc Pharmacol Ther

View full text Add to dashboard Cite

show abstract

“…Several in vitro and in vivo studies have reported that the activation of CB 1 and CB 2 can stimulate and inhibit NO production, disparately impacting the expression and activity of the NOS isoforms [12,16,22].…”

Section: Discussionmentioning

confidence: 99%

Distinct regulation of nNOS and iNOS by CB2 receptor in remote delayed neurodegeneration

et al. 2011

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Hemicerebellectomy results in remote delayed degeneration of precerebellar neurons. We have reported that such a lesion induces type 2 cannabinoid receptor (CB(2)) expression in precerebellar neurons and that stimulation of CB(2), but not CB(1), has neuroprotective effects. In this study, we found that in the same model, the CB(2) agonist JWH-015 enhances neuronal nitric oxide synthase (nNOS) expression in axotomized neurons and that CB(2)-mediated neuroprotection is abrogated by pharmacological inhibition of nNOS. JWH-015 prevented the axotomy-induced upregulation of inducible NOS (iNOS) in astrocytes but had no effect on endothelial NOS (eNOS). In addition, we observed that JWH-015 significantly reduces hemicerebellectomy-induced neuroinflammatory responses and oxidative/nitrative stress. With regard to the signaling pathways of CB(2)/nNOS-mediated neuroprotection, we noted nNOS-dependent modulation of the expression of anti-oxidative (Hsp70) and anti-apoptotic (Bcl-2) proteins. These findings shed light on the interactions between the endocannabinoid and nitrergic systems after focal brain injury, implicating distinct functions of nNOS activation and iNOS inhibition in CB(2) signaling, which protect neurons from axotomy-induced cell death.

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“…As reported before, cannabinoids protect the heart in several pathological conditions such as ischemia/reperfusion injury, myocardial infarction and also doxorubicin-induced cardiotoxicity [6,[8][9][10]. Cannabinoids bind to two classical receptors (CB 1 and CB 2 ) in mammalian tissues.…”

Section: Introductionmentioning

confidence: 91%

Peroxisome Proliferator-Activated Receptor-α Inhibition Protects Against Doxorubicin-Induced Cardiotoxicity in Mice

et al. 2015

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Doxorubicin is an effective chemotherapeutic drug against a considerable number of malignancies. However, its toxic effects on myocardium are confirmed as major limit of utilization. PPAR-α is highly expressed in the heart, and its activation leads to an increased cardiac fatty acid oxidation and cardiomyocyte necrosis. This study was performed to adjust the hypothesis that PPAR-α receptor inhibition protects against doxorubicin-induced cardiac dysfunction in mice. Male Balb/c mice were used in this study. Left atria were isolated, and their contractility was measured in response to electrical field stimulation in a standard organ bath. PPAR-α activity was measured using specific PPAR-α antibody in an ELISA-based system coated with double-strand DNA containing PPAR-α response element sequence. Moreover, cardiac MDA and TNF-α levels were measured by ELISA method. Following incubation with doxorubicin (35 µM), a significant reduction in atrial contractility was observed (P < 0.001). Pretreatment of animals with a selective PPAR-α antagonist, GW6471, significantly improved doxorubicin-induced atrial dysfunction (P < 0.001). Furthermore, pretreatment of the mice with a non-selective cannabinoid agonist, WIN55212-2, significantly decreased PPAR-α activity in cardiac tissue, subsequently leading to significant improvement in doxorubicin-induced atrial dysfunction (P < 0.001). Also, GW6471 and WIN significantly reduced cardiac MDA and TNF-α levels compared with animals receiving doxorubicin (P < 0.001). The study showed that inhibition of PPAR-α is associated with protection against doxorubicin-induced cardiotoxicity in mice, and cannabinoids can potentiate the protection by PPAR-α blockade. Moreover, PPAR-α may be considered as a target to prevent cardiotoxicity induced by doxorubicin in patients undergoing chemotherapy.

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Cannabinoid/agonist WIN 55,212‐2 reduces cardiac ischaemia–reperfusion injury in Zucker diabetic fatty rats: role of CB2 receptors and iNOS/eNOS

Cited by 44 publications

References 66 publications

Prospects for Creation of Cardioprotective Drugs Based on Cannabinoid Receptor Agonists

Prospects for Creation of Cardioprotective Drugs Based on Cannabinoid Receptor Agonists

Distinct regulation of nNOS and iNOS by CB2 receptor in remote delayed neurodegeneration

Peroxisome Proliferator-Activated Receptor-α Inhibition Protects Against Doxorubicin-Induced Cardiotoxicity in Mice

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