Effects of ACE inhibition on left ventricular failure and oxidative stress in dahl salt-sensitive rats

Hiroyuki Tsutsui, Tomomi Ide, Shunji Hayashidani, Shintaro Kinugawa, Nobuhiro Suematsu, Hideo Utsumi, Akira Takeshita

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24 Citations (Scopus)

Abstract

Dahl salt-sensitive (DS) rats fed high-salt diet exert compensated left ventricular (LV) hypertrophy and eventually develop heart failure. Oxidative stress has been shown to be involved in myocardial remodeling and failure and thus might play an important role in this transition from hypertrophy to failure. We measured the amount of reactive oxygen species (ROS) in the myocardium from DS rats by using electron spin resonance spectroscopy with 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl (hydroxy-TEMPO) and also examined the effects of chronic angiotensin-converting enzyme (ACE) inhibition on the transition. We divided DS rats (5 weeks old, 150-200 g) into three groups: low-salt (0.3% NaCl) diet for 10 weeks (LS group), high-salt (8% NaCl) diet for 10 weeks (HS-10+V group), and high-salt diet and cilazapril (10 mg/kg body weight per day) started after 5 weeks of high-salt diet and maintained for 5 weeks (HS-10+Cil group). Systolic blood pressure (mm Hg) was significantly elevated in the HS-10+V (229 ± 5) and HS-10+Cil (209 ± 5) groups compared with the LS group (141 ± 2). The amount of myocardial ROS was not changed after 5 weeks of high-salt diet, but significantly increased in HS-10+V rats compared with LS rats, and was abolished in the HS-10+Cil group. HS-10+V rats exerted the clinical signs of heart failure, including increased lung weight and pleural effusion, associated with LV hypertrophy and LV cavity dilatation. In the HS-10+Cil group, signs of heart failure were significantly attenuated despite only a modest reduction in systolic blood pressure (-20 mm Hg). The progression of LV failure after hypertrophy in high-salt-loaded DS hypertensive rats was associated with increased myocardial ROS, and ACE inhibitor could prevent this transition from compensated hypertrophy to failure.

Original languageEnglish
Pages (from-to)725-733
Number of pages9
JournalJournal of Cardiovascular Pharmacology
Volume37
Issue number6
DOIs
Publication statusPublished - 2001

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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