Endocannabinoids and the Cardiovascular System in Health and Disease

Abstract

The endocannabinoid system is widely distributed throughout the cardiovascular system. Endocannabinoids play a minimal role in the regulation of cardiovascular function in normal conditions, but are altered in most cardiovascular disorders. In shock, endocannabinoids released within blood mediate the associated hypotension through CB(1) activation. In hypertension, there is evidence for changes in the expression of CB(1), and CB(1) antagonism reduces blood pressure in obese hypertensive and diabetic patients. The endocannabinoid system is also upregulated in cardiac pathologies. This is likely to be cardioprotective, via CB(2) and CB(1) (lesser extent). In the vasculature, endocannabinoids cause vasorelaxation through activation of multiple target sites, inhibition of calcium channels, activation of potassium channels, NO production and the release of vasoactive substances. Changes in the expression or function of any of these pathways alter the vascular effect of endocannabinoids. Endocannabinoids have positive (CB(2)) and negative effects (CB(1)) on the progression of atherosclerosis. However, any negative effects of CB(1) may not be consequential, as chronic CB(1) antagonism in large scale human trials was not associated with significant reductions in atheroma. In neurovascular disorders such as stroke, endocannabinoids are upregulated and protective, involving activation of CB(1), CB(2), TRPV1 and PPARα. Although most of this evidence is from preclinical studies, it seems likely that cannabinoid-based therapies could be beneficial in a range of cardiovascular disorders.

Activation of Endocannabinoid Receptor 2 as a Mechanism of Propofol Pretreatment‐Induced Cardioprotection against Ischemia‐Reperfusion Injury in Rats

“…Secondly, the effects of endocannabinoid release on cardioprotection was only observed in vitro, but not in in vivo study. However, considering the fact that cardiac endocannabinoid signaling in vivo could be influenced by cardiomyocytes, other cardiac cells, circulation, and neuroendocrine states [55, 56], the results that could gained in in vivo results might be different from the findings in our in vitro study. Nevertheless, the findings gained in our in vitro study identified the downstream signaling pathways in association with CB2R activation and cardioprotection of propofol conditioning that may foster further mechanistic studies.…”

Endocannabinoids modulate Gq/11 protein-coupled receptor agonist-induced vasoconstriction via a negative feedback mechanism

“…Therefore, in various forms of hypertension, the eCB system becomes tonically active. This occurs by enhancing the vasorelaxant responses to eCBs, changes in plasma eCB concentration or alterations in the vascular expression of eCB system components, including up‐regulation of CB 1 receptors . It is worth mentioning that more research concerns the possible role of the eCB system in cardiovascular regulation in hypertension …”

The alpha-1A adrenergic receptor agonist A61603 reduces cardiac polyunsaturated fatty acid and endocannabinoid metabolites associated with inflammation in vivo

“…N-Palmitoyl taurine*, 1-(1-enyl-stearoyl)-GPE, Palmitoylethanolamide*, N-Stearoyltaurine*, Oleoyl Ethanolamide*, 1-palmitoyl GPG, 10-Nonadecenoic acid, 15-Methylpalmitate), 4 are involved in the endocannabinoid (EC) Pathway. The EC system consists of cannabinoid receptors and their endogenous neuromodulatory lipid ligands that collectively play long-recognized roles in the neurological and immunological systems 29 and recently have been identified in the heart 30 . We found a roughly 50% decrease in the abundance of the biologically active EC metabolites oleoyl ethanolamide, palmitoyl ethanolamide, N-stearoyltaurine, and N-palmitoyltaurine after treatment with A61603 (Figure 2).…”