The consumption of fish and omega-3 fatty acids has been associated with re
duced morbidity and mortality from coronary heart disease. The precise mech
anisms by which fatty acids modulate atherosclerotic vascular disease remai
n to be defined. Experimental evidence suggests that fatty acids alter the
function of the vascular endothelium, a metabolically active tissue that in
tegrates signals between the circulation and the vascular wall. This review
focuses on the effects of fatty acids on vascular endothelial nitric oxide
production. Endothelial-derived nitric oxide regulates several vascular wa
ll events that participate in the evolution of vascular disease. Impairment
of endothelial nitric oxide production has been demonstrated in a variety
of conditions such as smoking, diabetes, and hypertension that are risk fac
tors for atherosclerosis. Evidence is reviewed that supports the postulate
that both qualitative and quantitative alterations in circulating fatty aci
d species modulate vascular endothelial nitric oxide production. Although t
he mechanisms by which fatty acids alter vascular nitric oxide production r
emain obscure, fatty acid-mediated alterations in endothelial gene expressi
on present a promising area for future investigation.