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Role of Endothelium in Abnormal Cannabidiol-Induced Vasoactivity in Retinal Arterioles.
- 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.
- Subjects :
- Animals
Cannabidiol analogs & derivatives
Dose-Response Relationship, Drug
Endothelin-1 pharmacology
Piperidines pharmacology
Pyrazoles pharmacology
Receptor, Cannabinoid, CB1 antagonists & inhibitors
Receptor, Cannabinoid, CB2 antagonists & inhibitors
Swine
Vasodilation physiology
Arterioles drug effects
Cannabidiol pharmacology
Endothelium, Vascular physiology
Resorcinols pharmacology
Retinal Vessels drug effects
Vasodilation drug effects
Subjects
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