Role of endothelium in responses of vascular smooth muscle.

A FEW years ago, we discovered that the relaxation by acetylcholine (ACh) of isolated preparations of arteries precontracted by addition of an exogenous stimulating agent (e.g., norepinephrine) is strictly dependent on the presence of endothelial cells (Furchgott and Zawadzki, 1980a, 1980b; Furchgott et al., 1981; Furchgott, 1981). Our initial study was on the descending thoracic aorta of the rabbit (henceforth referred to as rabbit aorta), but it was soon found that the requirement for endothelial cells for relaxation by ACh applied in the case of isolated arteries from all mammalian species tested. Using rabbit aorta, we demonstrated that this endothelium-dependent relaxation by ACh is initiated by an action of this agent on a muscarinic receptor of the endothelial cells. We also successfully demonstrated that the action of ACh on this receptor stimulates the endothelial cells to release some factor (or factors) which then acts on the smooth muscle cells of the artery to cause them to relax (Furchgott and Zawadzki, 1980b; Furchgott et al., 1981).