Angiotensin II type 1 receptor blocker attenuates myocardial remodelling and preserves diastolic function in diabetic heart

Hiroyuki Tsutsui, Shoji Matsushima, Shintaro Kinugawa, Tomomi Ide, Naoki Inoue, Yukihiro Ohta, Takashi Yokota, Sanae Hamaguchi, Kenji Sunagawa

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Blockade of the renin-angiotensin system reduces cardiovascular morbidity and mortality in diabetic patients. Angiotensin II (Ang II) plays an important role in the structural and functional abnormalities of the diabetic heart. We investigated whether or not Ang II type 1 receptor blocker (ARB) could attenuate left ventricular (LV) remodeling in male mice with diabetes mellitus (DM) induced by the injection of streptozotocin (200 mg/kg, i.p.). Diabetic mice were treated with candesartan (1 mg/kg/day; DM+Candesartan, n=7) or vehicle (DM+Vehicle, n=7) for 8 weeks. Heart rate and aortic blood pressure were comparable between the groups. Normal systolic function was preserved in diabetic mice. In contrast diastolic function was impaired in DM+Vehicle and was improved in DM+Candesartan, as assessed by the deceleration time of the peak velocity of transmitral diastolic flow (40.3±0.3 vs. 37.3±0.5 ms, p<0.01) and the time needed for relaxation of 50% maximal LV pressure to baseline value (τ; 10.6±0.7 vs. 8.7±0.6 ms, p<0.05) without significant changes in heart rate and aortic blood pressure. Improvement of LV diastolic function was accompanied by the attenuation of myocyte hypertrophy, interstitial fibrosis and apoptosis in association with the expression of connective tissue growth factor (CTGF) and myocardial oxidative stress. Moreover, candesartan directly inhibited Ang II-mediated Induction of CTGF in cultured cardiac fibroblasts. ARB might be beneficial to prevent cardiac abnormalities in DM.

Original languageEnglish
Pages (from-to)439-449
Number of pages11
JournalHypertension Research
Volume30
Issue number5
DOIs
Publication statusPublished - May 1 2007

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Angiotensin II Type 1 Receptor Blockers
Diabetes Mellitus
Connective Tissue Growth Factor
Angiotensin II
Arterial Pressure
Heart Rate
Ventricular Remodeling
Deceleration
Congenital Heart Defects
Ventricular Pressure
Renin-Angiotensin System
Streptozocin
Left Ventricular Function
Muscle Cells
Hypertrophy
Oxidative Stress
Fibrosis
Fibroblasts
Apoptosis
Morbidity

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Angiotensin II type 1 receptor blocker attenuates myocardial remodelling and preserves diastolic function in diabetic heart. / Tsutsui, Hiroyuki; Matsushima, Shoji; Kinugawa, Shintaro; Ide, Tomomi; Inoue, Naoki; Ohta, Yukihiro; Yokota, Takashi; Hamaguchi, Sanae; Sunagawa, Kenji.

In: Hypertension Research, Vol. 30, No. 5, 01.05.2007, p. 439-449.

Research output: Contribution to journalArticle

Tsutsui, Hiroyuki ; Matsushima, Shoji ; Kinugawa, Shintaro ; Ide, Tomomi ; Inoue, Naoki ; Ohta, Yukihiro ; Yokota, Takashi ; Hamaguchi, Sanae ; Sunagawa, Kenji. / Angiotensin II type 1 receptor blocker attenuates myocardial remodelling and preserves diastolic function in diabetic heart. In: Hypertension Research. 2007 ; Vol. 30, No. 5. pp. 439-449.
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