Yuan Zong1,2, Xujiao Zhou3,2, Jingyi Cheng1,2, Jian Yu1,2, Jihong Wu3,2, Chunhui Jiang1,2,4. 1. Department of Ophthalmology and Vision Science, Eye and ENT Hospital, Fudan University, Shanghai, China. 2. Key Laboratory of Myopia of State Health Ministry, and Key Laboratory of Visual Impairment and Restoration of Shanghai, Shanghai, China. 3. Eye and ENT Hospital, State Key laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China. 4. Department of Ophthalmology, People's Hospital of Shanghai No. 5, Shanghai, China.
Abstract
BACKGROUND/AIMS: Cannabinoids are vasoactive substances that act as key regulators of arterial tone in the blood vessels supplying peripheral tissues and the central nervous system. We therefore investigated the effect of cannabinoids on retinal capillaries and pericytes. METHODS: The effects of cannabinoids on capillary diameters were determined using an ex vivo whole-mount rat retinal model. Western blotting, quantitative PCR, and immunohistochemistry were performed to explore the underlying mechanism. RESULTS: Endogenous cannabinoid 2-arachidonoylglycerol and anandamide and exogenous cannabinoid (R-(+)-WIN55212-2) dilated the noradrenaline-precontracted capillaries in a concentration-dependent manner (1 µM to 0.1 mM). The extent of vasorelaxation was positively correlated with changes in pericyte width. The effects of R-(+)-WIN55212-2 on vasorelaxation and pericyte width were inhibited by a cannabinoid receptor type-1 (CB1) antagonist, AM251 or rimonabant (SR141716A), the nitric oxide synthase inhibitor l-NAME, and the guanylate cyclase inhibitor ODQ. They were also abolished by the removal of the endothelium, but not by the cannabinoid receptor-2 antagonist SR144528, the endothelial cannabinoid receptor antagonist O-1918, or the cyclooxygenase inhibitor indomethacin. CONCLUSION: The exogenous cannabinoid R-(+)-WIN55212-2 promotes the vasorelaxation of pericyte-containing rat retinal capillaries. This effect of R-(+)-WIN55212-2 is dependent on CB1 and the nitric oxide-cyclic guanosine monophosphate pathway, and requires an intact endothelium.
BACKGROUND/AIMS: Cannabinoids are vasoactive substances that act as key regulators of arterial tone in the blood vessels supplying peripheral tissues and the central nervous system. We therefore investigated the effect of cannabinoids on retinal capillaries and pericytes. METHODS: The effects of cannabinoids on capillary diameters were determined using an ex vivo whole-mount rat retinal model. Western blotting, quantitative PCR, and immunohistochemistry were performed to explore the underlying mechanism. RESULTS: Endogenous cannabinoid2-arachidonoylglycerol and anandamide and exogenous cannabinoid (R-(+)-WIN55212-2) dilated the noradrenaline-precontracted capillaries in a concentration-dependent manner (1 µM to 0.1 mM). The extent of vasorelaxation was positively correlated with changes in pericyte width. The effects of R-(+)-WIN55212-2 on vasorelaxation and pericyte width were inhibited by a cannabinoid receptor type-1 (CB1) antagonist, AM251 or rimonabant (SR141716A), the nitric oxide synthase inhibitor l-NAME, and the guanylate cyclase inhibitor ODQ. They were also abolished by the removal of the endothelium, but not by the cannabinoid receptor-2 antagonist SR144528, the endothelial cannabinoid receptor antagonist O-1918, or the cyclooxygenase inhibitor indomethacin. CONCLUSION: The exogenous cannabinoidR-(+)-WIN55212-2 promotes the vasorelaxation of pericyte-containing rat retinal capillaries. This effect of R-(+)-WIN55212-2 is dependent on CB1 and the nitric oxide-cyclic guanosine monophosphate pathway, and requires an intact endothelium.
Authors: María de Los Ángeles Nuñez-Lumbreras; José Luis Castañeda-Cabral; María Guadalupe Valle-Dorado; Vicente Sánchez-Valle; Sandra Orozco-Suárez; Rosalinda Guevara-Guzmán; Iris Martínez-Juárez; Mario Alonso-Vanegas; Fruzsina Walter; Maria A Deli; Francia Carmona-Cruz; Luisa Rocha Journal: Front Behav Neurosci Date: 2021-01-20 Impact factor: 3.558