Home LiteratureArticle Details
PMID: 15131000 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

The complexities of the cardiovascular actions of cannabinoids.

British journal of pharmacology ·Vol. 142 ·No. 1 ·2004-05-00 ·Pages 20-6

Randall MD, Kendall DA, O'Sullivan S

Abstract

The cardiovascular actions of cannbinoids are complex. In general they cause vasorelaxation in isolated blood vessels, while in anaesthetised animals they cause multiphasic responses which involve an early bradycardia and long-lasting hypotension. However, in conscious animals, the picture is one of bradycardia followed by pressor responses. Clearly, the responses to cannabinoids are dependent on the experimental conditions and synthetic cannabinoids and endocannabinoids exhibit different pharmacologies. In terms of mechanisms involved in the vascular responses to cannabinoids, the following have been implicated: the involvement of 'classical' cannabinoid receptors, the involvement of a novel endothelial cannabinoid receptor, the release of nitric oxide, the release of endothelium-derived hyperpolarising factor (EDHF), the activation of vanilloid receptors, metabolism of endocannabinoids to vasoactive molecules, and both peripheral inhibition and central excitation of the sympathetic nervous system.

MeSH Terms
Animals Arachidonic Acids/metabolism,pharmacology Cannabinoids/metabolism,pharmacology Cardiovascular System/drug effects,metabolism Endocannabinoids Humans Polyunsaturated Alkamides Vasodilation/drug effects,physiology
Chemicals
Arachidonic Acids Cannabinoids Endocannabinoids Polyunsaturated Alkamides anandamide
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Randall Michael D
School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH. [email protected]
Kendall David A
O'Sullivan Saoirse
References (63)
63 references, click to expand
  1. Selective ligands and cellular effectors of a G protein-coupled endothelial cannabinoid receptor.
    Mol Pharmacol. 2003 Mar;63(3):699-705 PMID: 12606780
  2. The endothelial component of cannabinoid-induced relaxation in rabbit mesenteric artery depends on gap junctional communication.
    J Physiol. 1999 Oct 15;520 Pt 2:539-50 PMID: 10523421
  3. The peripheral sympathetic nervous system is the major target of cannabinoids in eliciting cardiovascular depression.
    Naunyn Schmiedebergs Arch Pharmacol. 2003 May;367(5):434-43 PMID: 12709782
  4. Endothelium-independent relaxation to cannabinoids in rat-isolated mesenteric artery and role of Ca2+ influx.
    Br J Pharmacol. 2003 Jun;139(3):585-97 PMID: 12788818
  5. Endocannabinoids protect the rat isolated heart against ischaemia.
    Br J Pharmacol. 2003 Jun;139(4):805-15 PMID: 12813004
  6. Cannabinoid modulation of peripheral autonomic and sensory neurotransmission.
    Eur J Pharmacol. 2003 Jul 4;472(1-2):1-21 PMID: 12860468
  7. Characterisation of the vasorelaxant properties of the novel endocannabinoid N-arachidonoyl-dopamine (NADA).
    Br J Pharmacol. 2004 Mar;141(5):803-12 PMID: 14769783
  8. Cannabinoids. II. Cardiovascular effects.
    J Pharmacol Exp Ther. 1980 Jul;214(1):131-8 PMID: 6771387
  9. Cannabinoid pharmacology.
    Pharmacol Rev. 1986 Jun;38(2):151-78 PMID: 3529128
  10. Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors.
    Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):14136-41 PMID: 10570211
  11. Cardiovascular effects of 2-arachidonoyl glycerol in anesthetized mice.
    Hypertension. 2000 Feb;35(2):679-84 PMID: 10679517
  12. Endocannabinoids and vascular function.
    J Pharmacol Exp Ther. 2000 Jul;294(1):27-32 PMID: 10871291
  13. Cannabinoids cause central sympathoexcitation and bradycardia in rabbits.
    J Pharmacol Exp Ther. 2000 Aug;294(2):707-13 PMID: 10900251
  14. Vanilloid receptors on capsaicin-sensitive sensory nerves mediate relaxation to methanandamide in the rat isolated mesenteric arterial bed and small mesenteric arteries.
    Br J Pharmacol. 2000 Aug;130(7):1483-8 PMID: 10928948
  15. Endocannabinoids as cardiovascular modulators.
    Chem Phys Lipids. 2000 Nov;108(1-2):159-68 PMID: 11106789
  16. Systemic and portal hemodynamic effects of anandamide.
    Am J Physiol Gastrointest Liver Physiol. 2001 Jan;280(1):G14-20 PMID: 11123193
  17. Involvement of cannabinoids in the cardioprotection induced by lipopolysaccharide.
    Br J Pharmacol. 2001 Feb;132(4):793-6 PMID: 11181418
  18. Regional differences in anandamide- and methanandamide-induced membrane potential changes in rat mesenteric arteries.
    J Pharmacol Exp Ther. 2001 Feb;296(2):322-8 PMID: 11160613
  19. The endocannabinoid anandamide is a direct and selective blocker of the background K(+) channel TASK-1.
    EMBO J. 2001 Jan 15;20(1-2):47-54 PMID: 11226154
  20. 2-Arachidonoylglycerol, a candidate of endothelium-derived hyperpolarizing factor.
    Eur J Pharmacol. 2001 Mar16;415(2-3):233-8 PMID: 11275004
  21. Blockade of effects of smoked marijuana by the CB1-selective cannabinoid receptor antagonist SR141716.
    Arch Gen Psychiatry. 2001 Apr;58(4):322-8 PMID: 11296091
  22. Regional haemodynamic responses to the cannabinoid agonist, WIN 55212-2, in conscious, normotensive rats, and in hypertensive, transgenic rats.
    Br J Pharmacol. 2001 Jun;133(3):445-53 PMID: 11375262
  23. Hemodynamic effects of cannabinoids: coronary and cerebral vasodilation mediated by cannabinoid CB(1) receptors.
    Eur J Pharmacol. 2001 Jul 6;423(2-3):203-10 PMID: 11448486
  24. Anandamide induces cardiovascular and respiratory reflexes via vasosensory nerves in the anaesthetized rat.
    Br J Pharmacol. 2001 Oct;134(3):655-63 PMID: 11588121
  25. Mechanisms of anandamide-induced vasorelaxation in rat isolated coronary arteries.
    Br J Pharmacol. 2001 Oct;134(4):921-9 PMID: 11606334
  26. Anandamide-induced relaxation of sheep coronary arteries: the role of the vascular endothelium, arachidonic acid metabolites and potassium channels.
    Br J Pharmacol. 2001 Nov;134(5):1003-12 PMID: 11682448
  27. Anandamide and methanandamide induce both vanilloid VR1- and cannabinoid CB1 receptor-mediated changes in heart rate and blood pressure in anaesthetized rats.
    Naunyn Schmiedebergs Arch Pharmacol. 2001 Dec;364(6):562-9 PMID: 11770012
  28. Evidence of a novel site mediating anandamide-induced negative inotropic and coronary vasodilatator responses in rat isolated hearts.
    Br J Pharmacol. 2002 Mar;135(5):1191-8 PMID: 11877326
  29. Characterization of vasorelaxant responses to anandamide in the rat mesenteric arterial bed.
    J Physiol. 2002 Mar 15;539(Pt 3):893-902 PMID: 11897858
  30. Complex regional haemodynamic effects of anandamide in conscious rats.
    Br J Pharmacol. 2002 Apr;135(8):1889-96 PMID: 11959791
  31. Anandamide-induced vasorelaxation in rabbit aortic rings has two components: G protein dependent and independent.
    Am J Physiol Heart Circ Physiol. 2002 Jun;282(6):H2046-54 PMID: 12003810
  32. Delta 9-tetrahydrocannabinol and cannabinol activate capsaicin-sensitive sensory nerves via a CB1 and CB2 cannabinoid receptor-independent mechanism.
    J Neurosci. 2002 Jun 1;22(11):4720-7 PMID: 12040079
  33. Cardiovascular pharmacology of anandamide.
    Prostaglandins Leukot Essent Fatty Acids. 2002 Feb-Mar;66(2-3):343-51 PMID: 12052048
  34. Influence of the CB(1) receptor antagonist, AM 251, on the regional haemodynamic effects of WIN-55212-2 or HU 210 in conscious rats.
    Br J Pharmacol. 2002 Jun;136(4):581-7 PMID: 12055136
  35. The role of gap junctions in mediating endothelium-dependent responses to bradykinin in myometrial small arteries isolated from pregnant women.
    Br J Pharmacol. 2002 Aug;136(8):1085-8 PMID: 12163339
  36. Mechanisms underlying tissue selectivity of anandamide and other vanilloid receptor agonists.
    Mol Pharmacol. 2002 Sep;62(3):705-13 PMID: 12181448
  37. Cardiovascular effects of cannabinoids.
    Pharmacol Ther. 2002 Aug;95(2):191-202 PMID: 12182966
  38. Cannabinoid modulation of sensory neurotransmission via cannabinoid and vanilloid receptors: roles in regulation of cardiovascular function.
    Life Sci. 2002 Oct 18;71(22):2577-94 PMID: 12354577
  39. Cardiovascular system effects of marijuana.
    J Clin Pharmacol. 2002 Nov;42(11 Suppl):58S-63S PMID: 12412837
  40. Cannabinoid receptor activation in the rostral ventrolateral medulla oblongata evokes cardiorespiratory effects in anaesthetised rats.
    Br J Pharmacol. 2003 Sep;140(2):384-94 PMID: 12970095
  41. Anandamide content and interaction of endocannabinoid/GABA modulatory effects in the NTS on baroreflex-evoked sympathoinhibition.
    Am J Physiol Heart Circ Physiol. 2004 Mar;286(3):H992-1000 PMID: 14615281
  42. Novel antagonist implicates the CB1 cannabinoid receptor in the hypotensive action of anandamide.
    Eur J Pharmacol. 1995 May 24;278(3):279-83 PMID: 7589169
  43. Anandamide and delta 9-THC dilation of cerebral arterioles is blocked by indomethacin.
    Am J Physiol. 1995 Dec;269(6 Pt 2):H1859-64 PMID: 8594893
  44. Mechanism of the hypotensive action of anandamide in anesthetized rats.
    Hypertension. 1996 Oct;28(4):682-6 PMID: 8843898
  45. Physiological and behavioural effects of the endogenous cannabinoid, arachidonylethanolamide (anandamide), in the rat.
    Br J Pharmacol. 1996 Sep;119(1):107-14 PMID: 8872363
  46. Cardiovascular effects of anandamide in anesthetized and conscious normotensive and hypertensive rats.
    Hypertension. 1997 May;29(5):1204-10 PMID: 9149688
  47. Production and physiological actions of anandamide in the vasculature of the rat kidney.
    J Clin Invest. 1997 Sep 15;100(6):1538-46 PMID: 9294122
  48. Involvement of a cannabinoid in endothelium-derived hyperpolarizing factor-mediated coronary vasorelaxation.
    Eur J Pharmacol. 1997 Sep 24;335(2-3):205-9 PMID: 9369375
  49. Activation of peripheral CB1 cannabinoid receptors in haemorrhagic shock.
    Nature. 1997 Dec 4;390(6659):518-21 PMID: 9394002
  50. A comparison of EDHF-mediated and anandamide-induced relaxations in the rat isolated mesenteric artery.
    Br J Pharmacol. 1997 Dec;122(8):1573-84 PMID: 9422801
  51. N-arachidonylethanolamide relaxation of bovine coronary artery is not mediated by CB1 cannabinoid receptor.
    Am J Physiol. 1998 Jan;274(1 Pt 2):H375-81 PMID: 9458889
  52. Anandamide and endothelium-derived hyperpolarizing factor act via a common vasorelaxant mechanism in rat mesentery.
    Eur J Pharmacol. 1998 Apr 3;346(1):51-3 PMID: 9617751
  53. Platelet- and macrophage-derived endogenous cannabinoids are involved in endotoxin-induced hypotension.
    FASEB J. 1998 Aug;12(11):1035-44 PMID: 9707176
  54. The actions of some cannabinoid receptor ligands in the rat isolated mesenteric artery.
    Br J Pharmacol. 1998 Oct;125(3):533-41 PMID: 9806337
  55. Carbachol, an acetylcholine receptor agonist, enhances production in rat aorta of 2-arachidonoyl glycerol, a hypotensive endocannabinoid.
    Eur J Pharmacol. 1998 Nov 27;362(1):R1-3 PMID: 9865537
  56. Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice.
    Science. 1999 Jan 15;283(5400):401-4 PMID: 9888857
  57. Mesenteric vasodilation mediated by endothelial anandamide receptors.
    Hypertension. 1999 Jan;33(1 Pt 2):429-34 PMID: 9931142
  58. Effect of the cannabinoid receptor agonist WIN55212-2 on sympathetic cardiovascular regulation.
    Br J Pharmacol. 1999 Jan;126(2):457-66 PMID: 10077239
  59. Inhibition of the production of endothelium-derived hyperpolarizing factor by cannabinoid receptor agonists.
    Br J Pharmacol. 1999 Feb;126(4):949-60 PMID: 10193775
  60. Cannabinoid CB1 receptor of cat cerebral arterial muscle functions to inhibit L-type Ca2+ channel current.
    Am J Physiol. 1999 Jun;276(6 Pt 2):H2085-93 PMID: 10362691
  61. Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide.
    Nature. 1999 Jul 29;400(6743):452-7 PMID: 10440374
  62. Cannabinoid CB1 receptors fail to cause relaxation, but couple via Gi/Go to the inhibition of adenylyl cyclase in carotid artery smooth muscle.
    Br J Pharmacol. 1999 Oct;128(3):597-604 PMID: 10516638
  63. Microinjection of a cannabinoid receptor antagonist into the NTS increases baroreflex duration in dogs.
    Am J Physiol Heart Circ Physiol. 2003 May;284(5):H1570-6 PMID: 12521935
Article Info
Journal
British journal of pharmacology
Abbr.
Br J Pharmacol
ISSN
0007-1188
Published
2004-05-00
Pages
20-6
Language
English
Region
England
NLM ID
7502536
PMCID
PMC1574918
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]