Human brain capillary endothelium: 2arachidonoglycerol (endocannabinoid) interacts with endothelin-1. Circ Res 87:323–327

Abstract—In brain, the regulatory mechanism of the endothelial reactivity to nitric oxide and endothelin-1 may involve Ca21, cytoskeleton, and vasodilator-stimulated phosphoprotein changes mediated by the cGMP/cGMP kinase system.1 Endothelium of human brain capillaries or microvessels is used to examine the interplay of endothelin-1 with the putative vasorelaxant 2-arachidonoyl glycerol, an endogenous cannabimimetic derivative of arachidonic acid. This study demonstrates that 2-arachidonoyl glycerol counteracts Ca21 mobilization and cytoskeleton rearrangement induced by endothelin-1. This event is independent of nitric oxide, cyclooxygenase, and lipoxygenase and is mediated in part by cannabimimetic CB1 receptor, G protein, phosphoinositol signal transduction pathway, and Ca21-activated K1 channels. The induced rearrangements of cellular cytoskeleton (actin or vimentin) are partly prevented by inhibition of protein kinase C or high levels of potassium chloride. The 2-arachidonoyl glycerol–induced phosphorylation of vasodilator-stimulated phosphoprotein is mediated by cAMP. These findings suggest that 2-arachidonoyl glycerol may contribute to the regulation of cerebral capillary and microvascular function. (Circ Res. 2000;87:323-327.) Key Words: brain endothelial function n 2-arachidonoglycerol n endothelin-1 n endothelium n cannabinoids An endogenous cannabinoid originally isolated from gutand brain, 2-arachidonoyl glycerol (2-AG), can be generated and released from blood and vascular cells.2–4 2-AG is an intrinsic physiological ligand for the cannabinoi