Prospects for Creation of Cardioprotective Drugs Based on Cannabinoid Receptor Agonists.
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, Δ9-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(+)channel is involved in the synthetic cannabinoid HU-210-induced cardiac resistance to ischemia/reperfusion injury. Cannabinoids inhibit Na(+)/Ca(2+)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.
Federal State Budgetary Scientific Institution, Research Institute for Cardiology, Tomsk, Russia.
Leonid N
LN
Maslov
School of Clinical Sciences, University of Bristol, Bristol, United Kingdom i.khaliulin@bristol.ac.uk.
Igor
I
Khaliulin
Department of Physiology, Hebei Medical University, Shijiazhuang, China.
Yi
Y
Zhang
Federal State Budgetary Scientific Institution, Research Institute for Cardiology, Tomsk, Russia.
Andrey V
AV
Krylatov
Federal State Budgetary Scientific Institution, Research Institute for Cardiology, Tomsk, Russia.
Natalia V
NV
Naryzhnaya
Institute for Drug Research, Hebrew University of Jerusalem, Ein Kerem, Jerusalem, Israel.
Raphael
R
Mechoulam
Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Pozzuoli, Italy.
Luciano
L
De Petrocellis
Department of Physiology, University of South Alabama, Mobile, AL, USA.
James M
JM
Downey
D000818:Animals; D063386:Cannabinoid Receptor Agonists / Q000627:therapeutic use*; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D015195:Drug Design; D063388:Endocannabinoids / Q000378:metabolism; D006801:Humans; D008024:Ligands; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists* / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D063386:Cannabinoid Receptor Agonists; D002317:Cardiovascular Agents; D063388:Endocannabinoids; D008024:Ligands; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2
cannabinoid receptor agonists; heart; ischemia/reperfusion injury