Atherosclerosis or lipoprotein-induced endothelial dysfunction. Potential mechanisms underlying reduction in EDRF/nitric oxide activity.

ctivation of endothelial cells by physical, chemi- cal, and hormonal stimuli can result in the release of a number of vasoactive mediators.1 Under physiological conditions, mediator release ap- pears to be balanced in favor of inhibitory factors such as endothelium-derived relaxing factor (EDRF, identified as nitric oxide) and prostacyclin (PGI2) (Figure EDRF-NO and PGI have important protective actions in the vascular wall: They are potent inhibitors of smooth muscle contraction and smooth muscle proliferation,14 and they also inhibit platelet aggregation, stimulate platelet disaggregation, and inhibit platelet or monocyte adhesion to the endothelial surface.25,6 The endothelial cells located at sites that are prone to atherosclerosis appear to be morphologically and functionally different from normal endothelial cells.7-10 These endothelial cells have a diminished protective role in the blood vessel wall and may actively promote the atherosclerotic process.8 Numerous studies have demonstrated that a dysfunction in the release of EDRF-NO appears to occur at an early stage in the atherosclerotic process in animals and hu- mans.'1-23 This impairment in EDRF-NO release may be associated with an increased release of endotheliumderived contracting factors (EDCFs),18'24 which are func- tional and chemical antagonists of The shift in the balance of endothelial mediators might contribute in part to the diminution in the protec- tive role of the endothelium and could predispose the blood vessel to vasospasm or to a further progression of the disease process.