Antiatherosclerotic activity of drugs in relation to nitric oxide function.

Many studies have shown that loss of endothelium-derived nitric oxide is a major factor of ischemic episodes in patients with coronary artery disease and there is increasing evidence to suggest that nitric oxide might exert antiatherosclerotic actions. Based on these concepts, the results of animal studies on the effects of lipid lowering drugs, antioxidants, angiotensin converting enzyme inhibitors, Ca2+ channel blockers, estrogens and agents which modulate nitric oxide bioavailability are presented and compared to the results of patient studies and clinical trials. In spite of encouraging results obtained with antioxidants in animals, clinical trials could only show a clear positive effect of vitamin E treatment on the outcome of cardiovascular disease. Angiotensin converting enzyme inhibitors can ameliorate endothelial dysfunction in coronary heart disease, but their impact on disease progression remains unclear. There is evidence that estrogen replacement therapy in post-menopausal women may increase the bioavailability of nitric oxide. Finally, improved endothelial function and plaque stability clearly contribute to the clinical benefits of lipid lowering interventions, statins in particular. Taken together, these studies lend support to the concept that improving endothelial function and nitric oxide release might serve as valuable elements in the prevention or therapy of cardiovascular disease.