Endothelial dysfunction induced by oxidized low-density lipoproteins in isolated mouse aorta: a comparison with apolipoprotein-E deficient mice

We characterized the acute effects of oxidized low-density lipoproteins (ox idized-LDL) on vascular reactivity in isolated aorta from wild-type C57BL/6 J mice, and compared these with the chronic alterations in vascular functio n observed in apolipoprotein-E gene knockout [ApoE(-/-)] mice fed a high-fa t diet, which results in hyperlipidemia and atherosclerosis. In the abdomin al (but not thoracic) aorta, oxidized-LDL (100 mug/ml) reduced relaxations induced by acetylcholine (10(-9) M-10(-5) M), which are mediated entirely b y nitric oxide (NO). The relaxations induced by the NO donor S-nitroso-N-ac etylpenicillamine (SNAP, 10(-8) M-10(-4) M), the cyclic GMP analogue 8-brom o cyclic GMP (100 muM) and the nonspecific vasodilator papaverine (100 muM) were not changed by oxidized-LDL. Native LDL had no effect on vasorelaxati ons. The attenuation of endothelium-dependent relaxations caused by oxidize d-LDL mimicked the endothelial dysfunction found in ApoE(-/-) mice. These r esults are consistent with the suggestion that oxidized-LDL has an importan t role in the pathogenesis of endothelial NO dysfunction associated with hy perlipidemia and atherosclerosis in these mice. (C) 2001 Elsevier Science B .V. All rights reserved.