Figure 16-8 Schematic representation of potential modes of regulation of vascular tone by endothelial cell-related mechanisms. Norepinephrine (NA), adenosine triphosphate (ATP), calcitonin gene-related peptide (CGRP), substance P (SP), and vasoactive intestinal polypeptide (VIP) can be released from nerves in the adventitia (ADV) to act on their respective receptors in the media (MED) to cause vasoconstriction or vasodilation. ATP, acetylcholine (ACh), 5-hydroxytryptamine (5-HT), and SP released from endothelial cells (END) by shear stress or hypoxia act on their receptors on endothelial cells to cause release of endothelium-derived relaxing factors (EDRF) or prostaglandins (PG), which act on smooth muscle to cause relaxation. In areas denuded of endothelial cells, opposite effects may be produced by receptors on the smooth muscle. α, noradrenaline receptor; M, muscarinic receptor; P_2x , P_2x -purinoceptor; P_2y , P_2y -purinoceptor. (From Lincoln J, Burnstock G: Neural-endothelial interactions in control of local blood flow. In Warren J [ed]: The Endothelium: An Introduction to Current Research. New York, Wiley-Liss, 1990, p 21.)