The Role of Endothelium in the Responses of Vascular Smooth Muscle to Drugs

Several years ago we accidentally discovered that relaxation of isolated prepa­ rations of arteries (rings, transverse strips, or helical strips) by acetylcholine (ACh) was strictly dependent on the presence of endothelial cells on the intimal surface of the preparations (1-3). This discovery helped resolve the paradox that ACh, a potent vasodilator of arteries in vivo, often produced no relaxation or even contraction of isolated preparations of arteries in vitro (4, 5). Apparent­ ly those isolated preparations that had failed to relax had had their endothelial cells unintentionally rubbed off during the course of their preparation for experiments. This discovery also led to the finding that a number of other agents, including some but not all of the most potent known endogenous vasodilators, also require endothelial cells to produce relaxation in isolated arteries. A number of laboratories are now engaged in research on various aspects of the endothelium-dependent relaxation of blood vessels by various agents. This review attempts to bring together the more important findings in this new area of research. A fuller description of early experimental results in this area obtained by the author and others is available in another recent review (6). The reader is also referred to that review for a discussion of a postulated role for endothelial cells in mediating or facilitating contractions of some blood vessels under special conditions.