Cardiovascular effects of cannabinoids.
The prototypic endocannabinoid, anandamide, and synthetic analogues have been shown to elicit pressor and depressor effects, bradycardia, vasorelaxation, and inhibition of neurotransmission in the central and peripheral nervous systems. Cannabinoid-mediated inhibition of neurotransmission is mediated by inhibition of voltage-gated Ca(2+) channels and adenylyl cyclase and activation of inwardly rectifying K(+) channels. The precise mechanisms underlying the vasorelaxant actions of cannabinoids are currently unclear, but might involve both receptor-dependent and -independent and endothelium-dependent and -independent pathways. Mechanisms proposed have included the release of endothelial autacoids, activation of myoendothelial gap junctions, activation of the Na(+) pump, activation of K(+) channels, inhibition of Ca(2+) channels, and activation of vanilloid receptors, leading to the release of sensory neurotransmitters. Pathophysiologically, the vasodilator actions of endocannabinoids have been implicated in the hypotension associated with both septic and haemorrhagic shock, but their physiological significance remains to be determined.
School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, UK. michael.randall@nottingham.ac.uk
Michael D
MD
Randall
David
D
Harris
David A
DA
Kendall
Vera
V
Ralevic
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids / Q000378:metabolism / Q000494:pharmacology*; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D063388:Endocannabinoids; D005231:Fatty Acids, Unsaturated / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D002317:Cardiovascular Agents; D063388:Endocannabinoids; D005231:Fatty Acids, Unsaturated; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C078814:anandamide