Diabetes mellitus accelerates left ventricular diastolic dysfunction through activation of the renin-angiotensin system in hypertensive rats

Shigefumi Fukui, Yoshihiro Fukumoto, Jun Suzuki, Kenya Saji, Jun Nawata, Tsuyoshi Shinozaki, Yutaka Kagaya, Jun Watanabe, Hiroaki Shimokawa

研究成果: Article査読

18 被引用数 (Scopus)

抄録

Diabetes mellitus (DM) is a major risk factor for heart failure, independent of coronary artery disease or hypertension (HT). Therefore, our study was designed to examine the mechanisms of DM-induced left ventricular (LV) diastolic dysfunction. In this study, we made five different 10-week treatment groups of Dahl salt-sensitive rats as follows: Control; a low-salt (0.5% NaCl) diet, HT; a high-salt (5% NaCl) diet, DM; a low-salt diet with streptozotocin (STZ) injection (30 mg kg-1 i.p.), HT+DM; a high-salt diet with STZ injection, and the Olmesartan group; a high-salt diet with STZ treated with an angiotensin receptor blocker, olmesartan (1 mg kg-1 day-1). Cardiac diastolic dysfunction with a preserved systolic function was noted in the HT group, and was most prominently noted in the HT+DM group, characterized by enhanced cardiac fibrosis, whereas the extent of HT and myocardial hypertrophy was comparable between the two groups. Myocardial expressions of collagen III, transforming growth factor-β2, angiotensin-converting enzyme (ACE), angiotensin II type-1 receptor and myocardial oxidative stress (evaluated by 4-hydroxy-2-nonenal-modified protein) were mostly enhanced in the HT+DM group. Importantly, there was a positive correlation between the extent of diastolic dysfunction and that of myocardial ACE expression. All these cardiac abnormalities induced by DM and HT were ameliorated in the olmesartan group. These results indicate that DM accelerates diastolic dysfunction in hypertensive heart disease through activation of the renin-angiotensin system, with subsequent inflammatory and oxidative stresses and myocardial fibrosis, suggesting that an inhibition of the system is effective for the treatment of diastolic dysfunction in this combined disorder.

本文言語English
ページ(範囲)472-480
ページ数9
ジャーナルHypertension Research
32
6
DOI
出版ステータスPublished - 2009
外部発表はい

ASJC Scopus subject areas

  • 内科学
  • 生理学
  • 循環器および心血管医学

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