Cardiovascular actions of cannabinoids and their generation during shock.
Marijuana is a widely abused recreational drug well known for its psychoactive properties. Cannabinoids, the active ingredients of marijuana, elicit their neurobehavioral effects by interacting with the CB1 cannabinoid receptor subtype, expressed primarily in the brain but also present in some peripheral tissues. A second receptor subtype, the CB2 receptor, is expressed on cells of the immune system and is thought to be responsible for the immunosuppressant effects of cannabinoids. Recently, endogenous lipidlike substances have been identified, including arachidonyl ethanolamide (anandamide) and 2-arachidonyl glyceride, that bind to cannabinoid receptors and mimic many of the neurobehavioral effects of plant-derived cannabinoids. Both plant-derived cannabinoids and the endogenous ligands have been shown to elicit hypotension and bradycardia via activation of peripherally located CB1 receptors. Possible underlying mechanisms include presynaptic CB1 receptor mediated inhibition of norepinephrine release from peripheral sympathetic nerve terminals, and/or direct vasodilation via activation of vascular cannabinoid receptors. The latter may also be the target of endocannabinoids of vascular endothelial origin. Recent studies indicate that a peripheral endogenous cannabinoid system in circulating macrophages and platelets is activated in hemorrhagic and septic shock and may contribute to the hypotension associated with these conditions via activation of vascular cannabinoid receptors. The potential role of this mechanism in human shock conditions is under investigation.
Wagner
J A
JA
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA.
Varga
K
K
Kunos
G
G
D000818:Animals; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids / Q000378:metabolism / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006801:Humans; D015394:Molecular Structure; D010944:Plants / Q000737:chemistry; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000378:metabolism; D012769:Shock / Q000378:metabolism*
D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug