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Endocannabinoids and the Cardiovascular System in Health and Disease
1Faculty of Medicine and Health Sciences, Division of Medical Sciences and Graduate Entry Medicine, School of Medicine, Royal Derby Hospital Centre, University of Nottingham, Room 4107, Uttoxeter Road, Derby, DE22 3DT, UK. S.Osullivan@nottingham.ac.uk.
Insights
The endocannabinoid system impacts cardiovascular health, playing a protective role in conditions like cardiac pathologies and stroke. Targeting this system with cannabinoid-based therapies may offer future cardiovascular treatments.
Area of Science:
- Cardiovascular Science
- Neuroscience
- Pharmacology
Background:
- The endocannabinoid system (ECS) is present throughout the cardiovascular system.
- ECS plays a minor role in normal cardiovascular function but is altered in various cardiovascular disorders.
- Endocannabinoids are implicated in conditions including shock, hypertension, cardiac pathologies, atherosclerosis, and neurovascular disorders.
Purpose of the Study:
- To review the role of the endocannabinoid system in cardiovascular function and disease.
- To explore the therapeutic potential of targeting the ECS for cardiovascular disorders.
Main Methods:
- Review of preclinical and clinical studies on the endocannabinoid system in cardiovascular contexts.
- Analysis of endocannabinoid involvement in shock, hypertension, cardiac pathologies, atherosclerosis, and stroke.
- Examination of cannabinoid receptor (CB1, CB2) roles and other targets (TRPV1, PPARα).
Main Results:
- Endocannabinoids mediate hypotension in shock via CB1 activation.
- CB1 antagonism shows potential in reducing blood pressure in hypertensive and diabetic patients.
- The ECS is upregulated and potentially cardioprotective in cardiac pathologies, involving CB1 and CB2.
- Endocannabinoids induce vasorelaxation through multiple vascular mechanisms.
- ECS has mixed effects on atherosclerosis progression, with CB1's negative impact potentially offset by limited clinical efficacy of antagonism.
- Endocannabinoids are protective in stroke via CB1, CB2, TRPV1, and PPARα activation.
Conclusions:
- The endocannabinoid system is significantly involved in cardiovascular regulation and disease.
- Cannabinoid-based therapies show promise for treating a range of cardiovascular disorders, including hypertension and stroke.
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.
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