Role of endothelium in abnormal cannabidiol-induced vasoactivity in retinal arterioles

Er-Ning Su, M.E. Kelly, Stephen Cringle, Dao-Yi Yu

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

© 2015 The Association for Research in Vision and Ophthalmology, Inc. Purpose. 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. Methods. 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. Results. 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. Conclusions. 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.
Original languageEnglish
Pages (from-to)4029-4037
JournalInvestigative Ophthalmology and Visual Science
Volume56
Issue number6
DOIs
Publication statusPublished - Jun 2015

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