Cannabinoid and lipid-mediated vasorelaxation in retinal microvasculature

The endocannabinoid system plays a role in regulation of vasoactivity in the peripheral vasculature; however, little is known about its role in regulation of the CNS microvasculature. This study investigated the pharmacology of cannabinoids and cannabimimetic lipids in the retinal microvasculature,...

Full description

Saved in:
Bibliographic Details
Published in:European journal of pharmacology 2014-07, Vol.735, p.105-114
Main Authors: MacIntyre, Jessica, Dong, Alex, Straiker, Alex, Zhu, Jiequan, Howlett, Susan E., Bagher, Amina, Denovan-Wright, Eileen, Yu, Dao-Yi, Kelly, Melanie E.M.
Format: Article
Language:English
Subjects:
Animals
Arachidonic Acids - pharmacology
Cannabinoid
Cannabinoids
Endothelin-1 - pharmacology
Frontal Lobe - metabolism
Glycine - analogs & derivatives
Glycine - pharmacology
GPR18
Lipids
Male
Microvasculature
Microvessels
Rats, Inbred F344
Receptors, Cannabinoid - genetics
Receptors, Cannabinoid - metabolism
Receptors, G-Protein-Coupled - genetics
Receptors, G-Protein-Coupled - metabolism
Resorcinols - pharmacology
Retina
Retina - drug effects
Retina - physiology
Retinal Vessels - drug effects
Retinal Vessels - physiology
RNA, Messenger - metabolism
Vasodilation - drug effects
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The endocannabinoid system plays a role in regulation of vasoactivity in the peripheral vasculature; however, little is known about its role in regulation of the CNS microvasculature. This study investigated the pharmacology of cannabinoids and cannabimimetic lipids in the retinal microvasculature, a CNS vascular bed that is autoregulated. Vessel diameter (edge detector) and calcium transients (fura-2) were recorded from segments of retinal microvasculature isolated from adult, male Fischer 344 rats. Results showed that abnormal cannabidiol (Abn-CBD), an agonist at the putative endothelial cannabinoid receptor, CBe, inhibited endothelin 1 (ET-1) induced vasoconstriction in retinal arterioles. These actions of Abn-CBD were independent of CB1/CB2 receptors and were not mediated by agonists for GPR55 or affected by nitric oxide synthase (NOS) inhibition. However, the vasorelaxant effects of Abn-CBD were abolished when the endothelium was removed and were inhibited by the small Ca2+-sensitive K channel (SKCa) blocker, apamin. The effects of the endogenous endocannabinoid metabolite, N-arachidonyl glycine (NAGly), a putative agonist for GPR18, were virtually identical to those of Abn-CBD. GPR18 mRNA and protein were present in the retina, and immunohistochemistry demonstrated that GPR18 was localized to the endothelium of retinal vessels. These findings demonstrate that Abn-CBD and NAGly inhibit ET-1 induced vasoconstriction in retinal arterioles by an endothelium-dependent signaling mechanism that involves SKCa channels. The endothelial localization of GPR18 suggests that GPR18 could contribute to cannabinoid and lipid-mediated retinal vasoactivity.
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2014.03.055