Nitric Oxide in Atherosclerosis

The importance of nitric oxide (NO·) in the regulation of vascular physiology and the pathophysiology of vascular diseases is now widely recognized. The discovery of NO· as a key molecule released by the endothelium to control vascular homeostasis stems from the finding of Furchgott and Zawadzki that an intact vascular endothelium is required for a vasodilator response to muscarinic agonists. These investigators found that in the presence of an intact endothelium, acetylcholine produces dose-dependent relaxation in isolated arterial segments by triggering the release of a potent vasodilator substance termed endothelium-derived relaxing factor (1). In contrast, when the endothelium is denuded, acetylcholine produces contraction owing to unopposed direct vasoconstrictor effects on vascular smooth muscle (1). Endothelium-derived relaxing factor (EDRF) was eventually identified as NO·, as both possess similar chemical and biological properties (2,3). The specific identity of EDRF has not been without controversy as it has been suggested that an S-nitrosated compound, S-nitroso-L-cysteine, is a more likely candidate molecule (4).