Endocannabinoid signaling processes are present in diverse organisms and in organisms 500 million years divergent in evolution. Cannabinoid receptor-1 expression (CB1), anandamide, and anandamide amidase have been found in invertebrates. Furthermore, this signaling system is coupled to constitutive nitric oxide synthase (cNOS)-derived nitric oxide (NO) release in both vertebrates and invertebrates, thereby regulating neural, immune, and vascular-like functions in these divergent organisms. In human endothelial cells from various blood vessels, CB1 immunoreactive components are present as is its coupling to anandamide-stimulated cNOS-derived NO production, which exerts an autoregulatory role on cNOS release. The modulation of vascular diameter and vascular tone represents a crucial point of interest in these pathways, and interactions between NO and the sympathetic nerve system are of importance, i.e, norepinephrine. Here, a possible association of NO and endocannabinoid signaling with the relaxation response, a physiological counterpart of the stress response, may exist.

Keywords: Arachidonic Acids - metabolism, Arachidonic Acids - pharmacology, Endocannabinoids, Endothelium, Vascular - drug effects, Endothelium, Vascular - metabolism, Evolution, Molecular, Fatty Acids, Unsaturated - metabolism, Immune System - drug effects, Immune System - physiology, Models, Biological, Muscle Relaxation - physiology, Nitric Oxide - physiology, Nitric Oxide Synthase - metabolism, Receptors, Drug - metabolism, Sympathetic Nervous System - drug effects, Sympathetic Nervous System - physiology