ATHEROSCLEROSIS: Currently regarded as a multifactorial disease, atherosclerosis involves several factor including: oxidized LDL, endothelial cells, macrophages, immune cells, vascular smooth muscle cells. The endothelium appears to play a key role through the production of vasomotor, antiaggregate and leukocyte antiadhesion molecules. NITRIC OXIDE: NO is one of the most important mediators of endothelial antiatherothrombotic functions. Loss of endothelial production, called "endothelial dysfunction", i.e. loss of endothelial vasorelaxing, antiaggregate and leukocyte antiadhesion properties, could lead to increased fatty streak formation and acute arterial events (thrombus formation, vascular spasm).
Animal experiments: Although animal models strongly suggest a major role for NO in the pathophysiology of atherosclerosis, human studies with nitrates have been disappointing to date. The local effect of NO is probably closely adapted to local conditions. Therefore, massive delivery of NO as is achieved with nitrates could not repair endothelial dysfunction.