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Endocannabinoids and the Cardiovascular System in Health and Disease

  • Saoirse Elizabeth O’SullivanEmail author
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

Artery Atherosclerosis Blood Blood pressure Blood–brain barrier Heart Hypertension Vein 

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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© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Faculty of Medicine and Health Sciences, Division of Medical Sciences and Graduate Entry Medicine, School of Medicine, Royal Derby Hospital CentreUniversity of NottinghamDerbyUK

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