title: 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.
authors.affiliation: Faculty 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.
authors.forename: Saoirse Elizabeth
authors.initials: SE
authors.lastname: O'Sullivan
mesh_terms: D000818:Animals; D063386:Cannabinoid Receptor Agonists / Q000627:therapeutic use; D063387:Cannabinoid Receptor Antagonists / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D002319:Cardiovascular System / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D063388:Endocannabinoids / Q000378:metabolism* / Q000627:therapeutic use; D006439:Hemodynamics; D006801:Humans; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D063388:Endocannabinoids; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2
keywords: Artery; Atherosclerosis; Blood; Blood pressure; Blood–brain barrier; Heart; Hypertension; Vein