Endocannabinoids in Cerebrovascular Regulation.

The cerebral blood flow (CBF) is tightly regulated by myogenic, endothelial, metabolic and neural mechanisms under physiological conditions, and a large body of recent evidence indicates that inflammatory pathways have a major influence on the cerebral blood perfusion in certain CNS disorders, like hemorrhagic and ischemic stroke, traumatic brain injury and vascular dementia. All major cell types involved in cerebrovascular control pathways (i.e. smooth muscle, endothelium, neurons, astrocytes, pericytes, microglia and leukocytes) are capable of synthesizing endocannabinoids and/or express some or several of their target proteins (i.e. the cannabinoid 1 and 2 receptors (CB1 and CB2) and the TRPV1 ion channel). Therefore, the endocannabinoid system may importantly modulate the regulation of cerebral circulation under physiological and pathophysiological conditions in a very complex manner. Experimental data accumulated since the late 1990s indicate that the direct effect of cannabinoids on cerebral vessels is vasodilation mediated, at least in part, by CB1 receptors. Cannabinoid-induced cerebrovascular relaxation involves both a direct inhibition of smooth muscle contractility and a release of vasodilator mediator(s) from the endothelium. However, under stress conditions (e.g. in conscious restrained animals or during hypoxia and hypercapnia) cannabinoid receptor activation was shown to induce a reduction of the CBF, probably via inhibition of the electrical and/or metabolic activity of neurons. Finally, in certain cerebrovascular pathologies (e.g. subarachnoid hemorrhage as well as traumatic and ischemic brain injury) activation of CB2 (and probably yet unidentified non-CB1/non-CB2) receptors appear to improve the blood perfusion of the brain via attenuating vascular inflammation.
Copyright © 2015, American Journal of Physiology – Heart and Circulatory Physiology.