Central regulation mechanisms of brain endocannabinoid-induced inhibitory effects on central activation of sympatho-adrenomedullary outflow

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We examined central regulation mechanisms of sympatho-adrenomedullary (SA) outflow, which plays an important role in pathophysiological responses to stressors, regarding brain 2-arachidonoylglycerol (2-AG), an endogenous ligand for cannabinoid receptors (endocannabinoid, eCB), and the hypothalamic paraventricular nucleus (PVN), a regulatory center of the outflow. The results from the present studies suggest that (1) brain 2-AG can be metabolized to prostaglandin E2 (PGE2) glycerol ester, thereby activating the SA outflow as a precursor of PGE2, and that (2) brain eCB can be suppressively involved in the central SA outflow in the PVN by inhibiting glutamate release from the glutamatergic nerves innervating the PVN. These findings indicate a possibility that drugs activating brain eCB signals may be beneficial for clinical application to "stress-related disorders", such as hypertension, developed by high levels of stress-induced excess activation of the SA outflow.