The Nature of Endothelium-Derived Relaxing Factor

Abstract

The phenomenon of endothelium-dependent relaxation, first described in detail by Furchgott and colleagues (Furchgott and Zawadzki, 1980), has now been demonstrated in a wide range of blood vessels from a variety of species studied, including human (for reviews, see Furchgott, 1983; Griffith et al., 1985a; Busse et al., 1985). Endothelium-dependent relaxation can be elicited in vivo (Angus et al., 1983) as well as in standard in vitro pharmacological preparations by a number of agents at pharmacological concentrations. The inhibitory potential of the endothelium on vascular smooth muscle can be potent enough to virtually abolish responses in some arteries (Fig. 1) (Griffith et al., 1984a). The important role of endothelium is further emphasized when considering that the total mass of endothelial cells in the human body is approximately equivalent to that of the liver (Gerlach et al., 1985). Initial investigations into the mechanisms by which the phenomenon occurred suggested that it was mediated by a humoral agent, on the basis of “sandwich” experiments in which an aortic strip with intact endothelium could be shown to relax a closely apposed strip in which the endothelium had been removed (Furchgott and Zawadzki, 1980).