R-(+)-WIN55212-2 protects pericytes from ischemic damage and restores retinal microcirculatory patency after ischemia/reperfusion injury

Biomed Pharmacother. 2023 Aug 10;166:115197. doi: 10.1016/j.biopha.2023.115197. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: 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 investigated the effects of cannabinoids on retinal capillaries and pericytes.

EXPERIMENTAL APPROACH: The effect of cannabinoids on capillary diameters was determined in an ex vivo whole-mount rat retinal model. Western blotting, quantitative PCR, and immunohistochemistry were performed to examine the underlying mechanism.

KEY RESULTS: Endogenous cannabinoids 2-arachidonoylglycerol and anandamide and exogenous cannabinoid (R-(+)-WIN55212-2) dilated noradrenaline-precontracted capillaries in a concentration-dependent manner (1 μM to 0.1 mM). The extent of vasorelaxation correlated positively 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.

CONCLUSIONS & IMPLICATIONS: 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.

PMID:37572634 | DOI:10.1016/j.biopha.2023.115197