Production of Nitric Oxide, but Not Prostacyclin, Is Reduced in Klotho Mice

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A novel murine model of aging (kl/kl mice) has been developed by in vivo mutagenesis. We analyzed endothelial function in this strain. Ring preparations of the thoracic aorta were obtained from 6- to 9-week old wild-type (+/+) and heterozygous (kl/+) klotho mice. The aortas of kl/+ mice showed an exaggerated contractile response to norepinephrine and attenuated vasodilator responses to acetylcholine and lecithinized superoxide dismutase (SOD) compared to +/+ mice. The response to sodium nitroprusside was unaltered in kl/+ mice. The contraction in response to norepinephrine was augmented by treatment with <i>N</i> <sup>G</sup>-nitro-<sc><font size = -2>L</font></sc>-arginine methyl ester (<sc><font size = -2>L</font></sc>-NAME, 10<sup>−</sup><sup>5</sup> M) to a greater extent in +/+ mice than in kl/+ mice. Treatment with <sc><font size = -2>L</font></sc>-NAME abolished the vasodilator responses to both acetylcholine and lecithinized SOD. NO metabolites (NO<sub>2</sub><sup>−</sup> and NO<sub>3</sub><sup>−</sup>) and cGMP concentrations in the urine were significantly reduced in kl/+ mice compared to +/+ mice. However, the urinary excretion of 6-keto-prostaglandin F<sub>1</sub><sub>α</sub> was unaltered. There was little immunostaining for NO synthase and vascular endothelial growth factor (VEGF) in the aorta of kl/+ mice. No immunostaining for NO synthase was noted in the aorta of kl/kl mice. The expression of the klotho gene product may have a role in the regulation of VEGF expression and is tightly linked to endothelial release of NO.

収録刊行物

  • The Japanese journal of pharmacology

    The Japanese journal of pharmacology 89(2), 149-156, 2002-06-01

    公益社団法人 日本薬理学会

参考文献:  19件中 1-19件 を表示

被引用文献:  1件中 1-1件 を表示

各種コード

  • NII論文ID(NAID)
    10008684076
  • NII書誌ID(NCID)
    AA00691188
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    00215198
  • NDL 記事登録ID
    6261977
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z53-D199
  • データ提供元
    CJP書誌  CJP引用  NDL  J-STAGE 
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