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Endocannabinoids and the Cardiovascular System in Health and Disease

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Part of the Handbook of Experimental Pharmacology book series (HEP,volume 231)

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 CB1 activation. In hypertension, there is evidence for changes in the expression of CB1, and CB1 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 CB2 and CB1 (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 (CB2) and negative effects (CB1) on the progression of atherosclerosis. However, any negative effects of CB1 may not be consequential, as chronic CB1 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 CB1, CB2, 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.

Keywords

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Abbreviations

2-AG:

2-Arachidonoylglycerol

AEA:

Anandamide

ARA-S:

N-arachidonoyl-L-serine

BBB:

Blood–brain barrier

CB1 :

Cannabinoid receptor 1

CB2 :

Cannabinoid receptor 2

COX:

Cyclooxygenase

eNOS:

Endothelial nitric oxide synthase

FAAH:

Fatty acid amide hydrolase

MAGL:

Monoacylglycerol lipase

NADA:

N-arachidonoyl dopamine

NO:

Nitric oxide

OEA:

Oleoylethanolamide

PEA:

Palmitoylethanolamide

PPAR:

Peroxisome proliferator-activated receptors

PTX:

Pertussis toxin

SHR:

Spontaneously hypertensive rat

TBI:

Traumatic brain injury

THC:

Delta-9-tetrahydrocannabinol

TRPV1:

Transient receptor potential vanilloid 1

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O’Sullivan, S.E. (2015). Endocannabinoids and the Cardiovascular System in Health and Disease. In: Pertwee, R. (eds) Endocannabinoids. Handbook of Experimental Pharmacology, vol 231. Springer, Cham. https://doi.org/10.1007/978-3-319-20825-1_14

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