['Endothelin (ET)-1 has proatherogenic properties, since ET receptor antagonists reduce atherosclerotic lesions in animals. However, we recently demonstrated that ET-1 and ET(B) receptors are increased in atherosclerotic lesions. To further examine the effects of ET(B) receptor antagonism on atherogenesis, we investigated the chronic effects of the nonselective ET(A)/ET(B) receptor antagonist SB209670 on the development of atherosclerosis in apolipoprotein E (ApoE)-deficient mice.', 'Ninety-four male mice (10 weeks of age) were randomly divided into four groups: mice fed a Western-type diet or a chow diet with SB209670 treatment (10 mg/kg/day) or placebo for 12 weeks.', 'In mice fed the Western-type diet, but not in mice fed the chow diet, treatment with SB209670 significantly attenuated the increase in plasma total cholesterol, predominantly in the very-low-density lipoprotein and intermediate-density lipoprotein fractions, without altering the plasma triglyceride level. Furthermore, treatment with SB209670 significantly reduced the extent of aortic atherosclerosis, by 53% in mice fed the Western-type diet and by 38% in mice fed the chow diet. Histological analysis revealed that SB209670 prevented the formation of atheromatous plaque lesions by inhibiting the fibroproliferative process.'] Does blockade of endothelin receptors reduce diet-induced hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice?