Production of nitric oxide, but not prostacyclin, is reduced in klotho mice

Tetsuya Nakamura, Yuichiro Saito, Yoshio Ohyama, Hiroaki Masuda, Hiroyuki Sumino, Makoto Kuro-o, Youichi Nabeshima, Ryozo Nagai, Masahiko Kurabayashi

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45 Scopus citations


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 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 NG-nitro-L-arginine methyl ester (L-NAME, 10-5 M) to a greater extent in +/+ mice than in kl/+ mice. Treatment with L-NAME abolished the vasodilator responses to both acetylcholine and lecithinized SOD. NO metabolites (NO2- and NO3-) and cGMP concentrations in the urine were significantly reduced in kl/+ mice compared to +/+ mice. However, the urinary excretion of 6-keto-prostaglandin F 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.

Original languageEnglish (US)
Pages (from-to)149-156
Number of pages8
JournalJapanese Journal of Pharmacology
Issue number2
StatePublished - 2002


  • Endothelium
  • Immunohistochemistry
  • Vascular tone

ASJC Scopus subject areas

  • Pharmacology


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