The nature of endothelium-derived vascular relaxant factor

• Published in: Nature (London) Vol. 308; no. 5960; p. 645
• Main Authors: Griffith, T M, Edwards, D H, Lewis, M J, Newby, A C, Henderson, A H
• Format: Journal Article
• Language: English
• Published: England 01.04.1984
• Subjects: Acetylcholine - pharmacology; Animals; Aorta, Thoracic - physiology; Calcimycin - pharmacology; Endothelium - drug effects; Endothelium - physiology; Kinetics; Muscle Contraction - drug effects; Muscle Relaxation - drug effects; Muscle, Smooth, Vascular - physiology; Nitric Oxide; Perfusion; Rabbits; Serotonin - pharmacology; Vasodilator Agents
• ISSN: 0028-0836
• DOI: 10.1038/308645a0

The existence of endothelium-derived vascular relaxant factor (EDRF) was postulated by Furchgott and colleagues when they observed that acetylcholine paradoxically relaxed preconstricted aortic strip preparations by an endothelium-dependent mechanism. This phenomenon has since been demonstrated in different blood vessels and mammalian species and it can be elicited by several other agents. EDRF has been thought to be a humoral agent, a lipoxygenase derivative and possibly a free radical. In the study reported here, by using aortic preparations from the rabbit, alone and in cascade experiments with isolated perfused coronary preparations, we demonstrate definitively that EDRF is a humoral agent. It is released from unstimulated aortic preparations containing endothelium, its release can be stimulated for prolonged periods by acetylcholine, and it is not a lipoxygenase derivative or free radical but an unstable compound with a carbonyl group at or near its active site.