Losartan modulates muscular capillary density and reverses thiazide diuretic-exacerbated insulin resistance in fructose-fed rats

Qi Guo, Takefumi Mori, Yue Jiang, Chunyan Hu, Yusuke Ohsaki, Yoshimi Yoneki, Takashi Nakamichi, Susumu Ogawa, Hiroshi Sato, Sadayoshi Ito

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The renin-angiotensin system (RAS) is involved in the pathogenesis of insulin sensitivity (IS). The role of RAS in insulin resistance and muscular circulation has yet to be elucidated. Therefore, this study sought to determine the mechanisms of angiotensin II receptor blockers (ARBs) and/or diuretics on IS and capillary density (CD) in fructose-fed rats (FFRs). Sprague-Dawley rats were fed either normal chow (control group) or fructose-rich chow for 8 weeks. For the last 4 weeks, FFRs were allocated to four groups: an FFR group and groups treated with the thiazide diuretic hydrochlorothiazide (HCTZ), with the ARB losartan, or both. IS was evaluated by the euglycemic hyperinsulinemic glucose clamp technique at week 8. In addition, CD in the extensor digitorum longus muscle was evaluated. Blood pressure was significantly higher in the FFRs than in the controls. HCTZ, losartan and their combination significantly lowered blood pressure. IS was significantly lower in the FFR group than in the controls and was even lower in the HCTZ group. Losartan alone or combined with HCTZ significantly increased IS. In all cases, IS was associated with muscular CD, but not with plasma adiponectin or lipids. These results indicate that losartan reverses HCTZ-exacerbated insulin resistance, which can be mediated through the modulation of muscular circulation in rats with impaired glucose metabolism.

Original languageEnglish
Pages (from-to)48-54
Number of pages7
JournalHypertension Research
Volume35
Issue number1
DOIs
Publication statusPublished - 2012 Jan 1

Keywords

  • angiotensin II receptor blocker
  • capillary density
  • insulin sensitivity
  • skeletal muscle
  • thiazide diuretic

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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