title: Losartan modulates muscular capillary density and reverses thiazide diuretic-exacerbated insulin resistance in fructose-fed rats.
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.
authors: Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Qi
authors: Q
authors: Guo
authors: Takefumi
authors: T
authors: Mori
authors: Yue
authors: Y
authors: Jiang
authors: Chunyan
authors: C
authors: Hu
authors: Yusuke
authors: Y
authors: Ohsaki
authors: Yoshimi
authors: Y
authors: Yoneki
authors: Takashi
authors: T
authors: Nakamichi
authors: Susumu
authors: S
authors: Ogawa
authors: Hiroshi
authors: H
authors: Sato
authors: Sadayoshi
authors: S
authors: Ito
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002196:Capillaries / Q000187:drug effects*; D005632:Fructose / Q000008:administration & dosage*; D015309:Glucose Clamp Technique; D006852:Hydrochlorothiazide / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D006852:Hydrochlorothiazide; D005632:Fructose; D019808:Losartan