Am J Physiol Heart Circ Physiol. 2007 Mar 23; [Epub ahead of
print]Cannabidiol attenuates high glucose-induced endothelial cell
inflammatory response and barrier disruption.Rajesh M, Mukhopadhyay P,
Batkai S, Hasko G, Liaudet L, Drel VR, Obrosova IG, Pacher P.
NIAAA, Laboratory Physiological Studies, National Institutes of
Health, Bethesda, Maryland, United States.
A non-psychoactive cannabinoid cannabidiol (CBD) has been shown to
exert potent anti-inflammatory and antioxidant effects, and has
recently been reported to lower the incidence of diabetes in non-obese
diabetic mice and preserve the blood-retinal barrier in experimental
diabetes. In this study we have investigated the effects of CBD on
high glucose (HG)-induced, mitochondrial superoxide generation, NF-
kappaB activation, nitrotyrosine formation, iNOS and adhesion
molecules ICAM-1 and VCAM-1 expression, monocyte-endothelial adhesion,
transendothelial migration of monocytes, and disruption of endothelial
barrier function in human coronary artery endothelial cells (HCAECs).
HG markedly increased mitochondrial superoxide generation (measured by
flow cytometry using MitoSOX), NF-kappaB activation, nitrotyrosine
formation, up-regulation of iNOS and adhesion molecules ICAM-1 and
VCAM-1, transendothelial migration of monocytes, and monocyte-
endothelial adhesion in HCAECs. HG also decreased endothelial barrier
function measured by increased permeability and diminished expression
of VE-Cadherin in HCAECs. Remarkably, all the above mentioned effects
of HG were attenuated by CBD pretreatment. Since disruption of the
endothelial function and integrity by high glucose is a crucial early
event underlying the development of various diabetic complications,
our results suggest that CBD, which has recently been approved for the
treatment of inflammation, pain and spasticity associated with
multiple sclerosis in humans, may be of significant therapeutic
benefits against diabetic complications and atherosclerosis. Key
words: vascular, inflammation, oxidative stress, peroxynitrite,
cannabidiol.
PMID: 17384130 [PubMed - as supplied by publisher]
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