“Preventive treatment with cannabinoid agonists has been reported to reduce the infarct size in a mouse model of myocardial ischemia/reperfusion.
Here we investigated the possible cardioprotective effect of selective CB(2) cannabinoid receptor activation during ischemia.
Our data suggest that administration during ischemia reduces the infarct size in a mouse model of myocardial ischemia/reperfusion through a direct cardioprotective activity on cardiomyocytes and neutrophils.”
“Post-myocardial infarction (MI) heart failure is a major public health problem in Western countries and results from ischemia/reperfusion (IR)-induced cell death, remodeling, and contractile dysfunction.
Ex vivo studies have demonstrated the cardioprotective anti-inflammatory effect of the cannabinoid type 2 (CB2) receptor agonists within hours after IR.
Herein, we evaluated the in vivo effect of CB2 receptors on IR-induced cell death, fibrosis, and cardiac dysfunction and investigated the target role of cardiac myocytes and fibroblasts… CB2 receptor activation may protect against post-IR heart failure through direct inhibition of cardiac myocyte and fibroblast death and prevention of myofibroblast activation…
In conclusion, modulation of the endocannabinoid system is emerging as a novel approach for the therapy of various inflammatory, metabolic, cardiovascular, hepatic, and neurodegenerative disorders.
CB1 receptors exert cardioprotective effects in cirrhotic rats and against doxorubicin toxicity. Pharmacological inhibition of the endocannabinoid degradative pathway, fatty acid aminohydrolase, represents a novel protective strategy against chronic inflammation, oxidative and nitrative stresses, and apoptosis associated with cardiovascular aging and atherosclerosis.
CB2 receptor activation is thought to be anti-inflammatory and involved in protective mechanisms during atherosclerosis. In addition, selective CB2 agonists protect against cerebral and hepatic IR injuries.
We demonstrated a highly protective role of CB2 receptors in post-IR cardiac remodeling, potentially related to activation of antiapoptotic, prosurvival, and antifibrogenic pathways.
Our results infer that CB2 agonists may be useful in preventing reperfusion injury in acute coronary syndrome and provide novel evidence for the pivotal role of CB2 receptors in post-IR-induced cardiomyopathy.”
“Although cannabinoids have been recreationally employed for thousands of years, it was not until the discovery of their specific receptors, in the early nineties, that the molecular basis of cannabinoid activity have began to be understood.
Growing research in this field has demonstrated not only that the action of cannabinoids in mammals is mainly receptor-mediated, but also that endogenous cannabinoids, such as anandamide, are produced, metabolized, and taken up across the cell membrane through a facilitated uptake process.
The exogenous administration of cannabinoids, as well as the manipulation of their endogenous levels have been related to a variety of effects, such as analgesia, (temporary) impairment of cognition and learning, appetite enhancement and peripheral vasodilation.
Hence, the endocannabinoid system, including the CB1 and CB2 receptors, the metabolizing enzyme fatty acid amide hydrolase and the anandamide transporter, is a potential target for the development of novel therapeutic drugs in the treatment of various conditions, such as pain, feeding disorders and vascular disease among others.
Although most of the research in the field of cannabinoids has been focused on their effects in the central nervous system, a growing line of evidence indicates that cannabinoids can also play a major role in the control of physiopathological functions in the cardiovascular system.
In this context, endocannabinoids have been proposed as novel possible hypotensive agents, and have been involved in the hypotension observed in septic shock, acute myocardial infarction and cirrhosis. In addition, a protective role for endocannabinoids has been described in ischemia.”
“The psychoactive properties of cannabinoids, the biologically active constituents of the marijuana plant, have long been recognized. Recent research has revealed that cannabinoids elicit not only neurobehavioral, and immunological, but also profound cardiovascular effects.
Similar effects can be elicited by the endogenous ligand arachidonyl ethanolamine (anandamide) and 2-arachidonoyl-glycerol.
The biological effects of cannabinoids are mediated by specific receptors.
Two cannabinoid receptors have been identified so far: CB1-receptors are expressed by different cells of the brain and in peripheral tissues, while CB2-receptors were found almost exclusively in immune cells.
Through the use of a selective CB1 receptor antagonist and CB1 receptor-knockout mice the hypotensive and bradycardic effects of cannabinoids in rodents could be attributed to activation of peripheral CB1 receptors. In hemodynamic studies using the radioactive microsphere technique in anesthetized rats, cannabinoids were found to be potent CB1-receptor dependent vasodilators in the coronary and cerebrovascular beds.
Recent findings implicate the endogenous cannabinoid system in the pathomechanism of haemorrhagic, endotoxic and cardiogenic shock.
Finally, there is evidence that the extreme mesenteric vasodilation, portal hypertension and systemic hypotension present in advanced liver cirrhosis are also mediated by the endocannabinoid system.
These exciting, recent research developments indicate that the endogenous cannabinoid system plays an important role in cardiovascular regulation, and pharmacological manipulation of this system may offer novel therapeutic approaches in a variety of pathological conditions.”
“Cannabinoids include not only plant-derived compounds (of which delta9-tetrahydrocannabinol is the primary psychoactive ingredient of cannabis), but also synthetic agents and endogenous substances termed endocannabinoids which include anandamide (2-arachidonoylethanolamide) and 2-arachidonoylglycerol.
Cannabinoids act on specific, G-protein-coupled, receptors which are currently divided into two types, CB1 and CB2. Relatively selective agonists and antagonists for these receptors have been developed, although one agent (SR141716A) widely used as an antagonist at CB1 receptors has non-cannabinoid receptor-mediated effects at concentrations which are often used to define the presence of the CB1 receptor.
Both cannabinoid receptors are primarily coupled to Gi/o proteins and act to inhibit adenylyl cyclase. Stimulation of CB1 receptors also modulates the activity of K+ and Ca2+ channels and of protein kinase pathways including protein kinase B (Akt) which might mediate effects on apoptosis. CB, receptors may activate the extracellular signal-regulated kinase cascade through ceramide signalling.
Cannabinoid actions on the cardiovascular system have been widely interpreted as being mediated by CB1 receptors although there are a growing number of observations, particularly in isolated heart and blood vessel preparations, that suggest that other cannabinoid receptors may exist.
Interestingly, the currently identified cannabinoid receptors appear to be related to a wider family of lipid receptor, those for the lysophospholipids, which are also linked to Gi/o protein signalling.
Anandamide also activates vanilloid VR1 receptors on sensory nerves and releases the vasoactive peptide, calcitonin gene-related peptide (CGRP), which brings about vasodilatation through its action on CGRP receptors.
Current evidence suggests that endocannabinoids have important protective roles in pathophysiological conditions such as shock and myocardial infarction.
Therefore, their cardiovascular effects and the receptors mediating them are the subject of increasing investigative interest.”
“Interest in cannabinoid pharmacology developed rapidly since the discovery of cannabinoids receptors and endocannabinoids. Modulation of this system is becoming a hot topic in cardiovascular pharmacology mainly at the light of recent findings.
Among them, cardiac effects of cannabinoids were described with respect to their probable participation to the well-studied preconditioning phenomenon.
Beneficial effects of post-infarction cannabinoids administration against ischemia-reperfusion injury were also reported.
Finally, pathological situations concerning the cardiovascular system and including brain ischemia, hemorrhagic and endotoxic shocks were reported to be linked with endocannabinoids.
However, the clinical use of cannabinoid receptors agonists or antagonists will depend on the development of non psychoactive compounds.”
“Endocannabinoids are bioactive amides, esters, and ethers of long-chain polyunsaturated fatty acids.
Evidence suggests that activation of the endocannabinoid pathway offers cardioprotection against myocardial ischemia, arrhythmias, and endothelial dysfunction of coronary arteries.
In conclusion, CB-13 inhibits cardiomyocyte hypertrophy through AMPK-eNOS signaling and may represent a novel therapeutic approach to cardioprotection.”
“Ischemic heart disease is associated with inflammation, interstitial fibrosis and ventricular dysfunction prior to the development of heart failure.
Endocannabinoids and the cannabinoid receptor CB2 have been claimed to be involved, but their potential role in cardioprotection is not well understood. We therefore explored the role of the cannabinoid receptor CB2 during the initial phase of ischemic cardiomyopathy development prior to the onset of ventricular dysfunction or infarction.
… the endocannabinoid-CB2 receptor axis plays a key role in cardioprotection during the initial phase of ischemic cardiomyopathy development.”
“The cardioprotective effect of HU-210 remained unchanged under condition of NO synthase inhibition.
The results of the experiment suggest that the cardioprotective effect of HU-210 can be determined by a decrease in cAMP level in the myocardium during reperfusion. cGMP and NO synthase do not contribute to cytoprotective effect of HU-210.”
“The aim of the present article is to review the cardioprotective properties of cannabinoids, with an emphasis on the signaling pathways involved.
Cannabinoids have been reported to protect against ischemia in rat isolated hearts, as well as in rats and mice in vivo.
Finally, although nitric oxide (NO) was shown to exert both pro and anti-apoptotic effects on cardiomyocytes, with an apparently controversial effect on myocardial survival, our data suggest that NO may contribute to the cardioprotective effect of some cannabinoids.”
https://www.jstage.jst.go.jp/article/jphs/102/2/102_2_155/_article