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Role of Endothelium in Abnormal Cannabidiol-Induced Vasoactivity in Retinal Arterioles.

Authors :
Su EN
Kelly ME
Cringle SJ
Yu DY
Source :
Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2015 Jun; Vol. 56 (6), pp. 4029-37.
Publication Year :
2015

Abstract

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.<br />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.<br />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.<br />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.

Details

Language :
English
ISSN :
1552-5783
Volume :
56
Issue :
6
Database :
MEDLINE
Journal :
Investigative ophthalmology & visual science
Publication Type :
Academic Journal
Accession number :
26098470
Full Text :
https://doi.org/10.1167/iovs.14-14879