-Dietary flaxseed has significant anti-atherogenic effects. However, the limits of this action and its effects on vascular contractile function are not known. We evaluated the effects of flaxseed supplementation on atherosclerosis and vascular function under prolonged hypercholesterolemic conditions in New Zealand White rabbits assigned to one of four groups for 6, 8, or 16 wk of feeding: regular diet (RG), 10% flaxseed-supplemented diet (FX), 0.5% cholesterol-supplemented diet (CH), and 0.5% cholesterol-and 10% flaxseed-supplemented diet (CF). Cholesterol feeding resulted in elevated plasma cholesterol levels and the development of atherosclerosis. The CF group had significantly less atherosclerotic lesions in the aorta and carotid arteries after 6 and 8 wk than the CH animals. However, the antiatherogenic effect of flaxseed supplementation was completely attenuated by 16 wk. Maximal tension induced in aortic rings either by KCl or norepinephrine was not impaired by dietary cholesterol until 16 wk. This functional impairment was not prevented by including flaxseed in the high-cholesterol diet. Aortic rings from the cholesterol-fed rabbits exhibited an impaired relaxation response to acetylcholine at all time points examined. Including flaxseed in the high-cholesterol diet completely normalized the relaxation response at 6 and 8 wk and partially restored it at 16 wk. No significant changes in the relaxation response induced by sodium nitroprusside were observed in any of the groups. In summary, dietary flaxseed is a valuable strategy to limit cholesterol-induced atherogenesis as well as abnormalities in endothelial-dependent vasorelaxation. However, these beneficial effects were attenuated during prolonged hypercholesterolemic conditions. linseed; acetylcholine; nutrition; polyunsaturated fatty acids; vascular relaxation ATHEROSCLEROSIS IS THE leading cause of cardiovascular morbidity and mortality in North America (77). Atherosclerosis induces two significant pathological processes: an ischemic event due to blood flow obstruction and vascular contractile dysfunction. It is well known that atherosclerosis is associated with elevated circulating cholesterol levels. Elevated plasma cholesterol concentrations induced by cholesterol feeding result in the development of atherosclerosis and an impairment in endothelium-dependent vasodilation in rabbits (9,26,29,30,36). The development of interventions to inhibit cholesterolinduced atherosclerosis and the associated vascular dysfunction have received much attention because of this strong association. For example, there is an increasing interest in nutritional interventions that may prevent the development of atherosclerosis and protect against the vascular function abnormalities induced by cholesterol consumption. Flaxseed is one such novel dietary intervention. Flaxseed is a good source of soluble and insoluble dietary fiber and is the richest plant source of ␣-linolenic acid [ALA; C18:3 n-3, omega-3 (n-3) fatty acid] as well as the lignan secoisolariciresinol digluco...

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