Troglitazone improves endothelial function and augments renal klotho mRNA expression on Otsuka Long-Evans Tokushima Fatty (OLETF) rats with multiple atherogenic risk factors

T. Yamagishi, Y. Saito, T. Nakamura, S. I. Takeda, H. Kanai, H. Sumino, M. Kuro-O., Y. I. Nabeshima, M. Kurabayashi, R. Nagai

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Targeted disruption of the klotho gene induces multiple phenotypes characteristic of human aging, including arteriosclerosis, pulmonary emphysema and osteoporosis. Moreover, we previously observed that insufficient klotho expression in mice leads to endothelial dysfunction. In the present study, we used Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which exhibit hypertension, obesity, severe hyperglycemia and hypertriglyceridemia, and are thus considered an animal model of atherogenic disease, to test the effects of oral administration of troglitazone (200 mg/kg) on renal klotho mRNA expression and endothelial function. Systolic blood pressure, body weight, plasma glucose and triglyceride levels were all significantly higher in 30-week-old OLETF rats than in controls (LETO; Long-Evans Tokushima Otsuka) (p<0.05, n=7). In addition, endothelium-dependent relaxation of the aorta in response to 10-5 M acetylcholine was significantly attenuated in OLETF rats (p<0.05, n=7), as was renal expression of klotho mRNA. Administration of troglitazone for 10 weeks significantly reduced systolic blood pressure, plasma glucose and triglyceride levels in OLETF rats, while augmenting endothelium-dependent aortic relaxation and renal klotho mRNA expression. These findings suggest that troglitazone protects the vascular endothelium against damage caused by the presence of multiple atherogenic factors.

Original languageEnglish (US)
Pages (from-to)705-709
Number of pages5
JournalHypertension Research
Volume24
Issue number6
DOIs
StatePublished - Dec 24 2001

Keywords

  • Diabetes mellitus
  • Endothelium
  • Hyperlipidemia
  • Hypertension
  • Klotho

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Yamagishi, T., Saito, Y., Nakamura, T., Takeda, S. I., Kanai, H., Sumino, H., Kuro-O., M., Nabeshima, Y. I., Kurabayashi, M., & Nagai, R. (2001). Troglitazone improves endothelial function and augments renal klotho mRNA expression on Otsuka Long-Evans Tokushima Fatty (OLETF) rats with multiple atherogenic risk factors. Hypertension Research, 24(6), 705-709. https://doi.org/10.1291/hypres.24.705