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Er-Ning Su, Melanie E. Kelly, Stephen J. Cringle, Dao-Yi Yu; Role of Endothelium in Abnormal Cannabidiol-Induced Vasoactivity in Retinal Arterioles. Invest. Ophthalmol. Vis. Sci. 2015;56(6):4029-4037. doi: https://doi.org/10.1167/iovs.14-14879.
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© ARVO (1962-2015); The Authors (2016-present)
Cannabinoids have been reported to mediate changes in vascular resistance through endothelial receptor targets. We examined involvement of the endothelium in cannabinoid-mediated vasoactive responses in resistance arterioles of the retina.
Vascular responses to both intraluminal (IL) and extraluminal (EL) administration of the atypical cannabinoid, abnormal cannabidiol (abn-CBD), a prototypical agonist at the non-CB1/CB2 endothelial cannabinoid receptor (CBeR), were studied in endothelial intact and endothelial denuded, isolated perfused porcine retinal arterioles with and without endothelin-1 (ET-1) precontraction. The effects of AM251, a CB1 receptor antagonist, and O-1918, an analog of CBD reported to antagonize CBeR, were also studied.
Dose-dependent vasocontractile responses were induced by both IL and EL administration of abn-CBD in the absence of precontraction. Significantly greater vasoconstriction was induced by IL administration of abn-CBD than with EL administration. In contrast, only vasodilation to abn-CBD was observed in ET-1 precontracted retinal arterioles. Endothelium removal significantly reduced abn-CBD–induced vasoactivity when abn-CBD was used IL but not when applied EL. IL abn-CBD–induced vasoactivity was antagonized by O-1918 and AM251.
Cannabinoids show complex vasoactive actions in isolated perfused retinal arterioles. The fact that abn-CBD-mediated vasorelaxation was seen only in precontracted retinal vessels indicates that the abn-CBD–induced vasoactive response is highly dependent on vascular tone. Furthermore, IL and EL administration produced differential responses, and removal of endothelium blunted abn-CBD vasoactivity, highlighting the critical role of endothelium in abn-CBD vasoactivity. AM251 and O-1918 inhibition of abn-CBD–induced vasoactivity suggests the possibility of modulating abn-CBD–induced vasoactivity.
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