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

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      European Journal of Pharmacology
      Elsevier BV

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          Abstract

          We characterized the acute effects of oxidized low-density lipoproteins (oxidized-LDL) on vascular reactivity in isolated aorta from wild-type C57BL/6J mice, and compared these with the chronic alterations in vascular function observed in apolipoprotein-E gene knockout [ApoE(-/-)] mice fed a high-fat diet, which results in hyperlipidemia and atherosclerosis. In the abdominal (but not thoracic) aorta, oxidized-LDL (100 microg/ml) reduced relaxations induced by acetylcholine (10(-9) M-10(-5) M), which are mediated entirely by nitric oxide (NO). The relaxations induced by the NO donor S-nitroso-N-acetylpenicillamine (SNAP, 10(-8) M-10(-4) M), the cyclic GMP analogue 8-bromo cyclic GMP (100 microM) and the nonspecific vasodilator papaverine (100 microM) were not changed by oxidized-LDL. Native LDL had no effect on vasorelaxations. The attenuation of endothelium-dependent relaxations caused by oxidized-LDL mimicked the endothelial dysfunction found in ApoE(-/-) mice. These results are consistent with the suggestion that oxidized-LDL has an important role in the pathogenesis of endothelial NO dysfunction associated with hyperlipidemia and atherosclerosis in these mice.

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          Author and article information

          Journal
          European Journal of Pharmacology
          European Journal of Pharmacology
          Elsevier BV
          00142999
          July 2001
          July 2001
          : 424
          : 2
          : 141-149
          Article
          10.1016/S0014-2999(01)01140-2
          11476760
          d55930f2-532d-4edd-8a21-927e52244468
          © 2001

          https://www.elsevier.com/tdm/userlicense/1.0/

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