Effects of ACE inhibition on left ventricular failure and oxidative stressin Dahl salt-sensitive rats

Dahl salt-sensitive (DS) rats fed high-salt diet exert compensated left ven tricular (LV) hypertrophy and eventually develop heart failure. Oxidative s tress has been shown to be involved in myocardial remodeling and failure an d thus might play an important role in this transition from hypertrophy to failure. We measured the amount of reactive oxygen species (ROS) in the myo cardium from DS rats by using electron spin resonance spectroscopy with 4-h ydroxy-2,2,6,6-tetramethyl-piperidine (hydroxy-TEMPO) and also examined the effects of chronic angiotensin-converting enzyme (ACE) inhibition on the t ransition. We divided DS rats (5 weeks old, 150-200 g) into three groups: l ow-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 b ody 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 signific antly 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 no t changed after 5 weeks of high-salt diet, but significantly increased in H S-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 incre ased lung weight and pleural effusion, associated with LV hypertrophy and L V cavity dilatation. In the HS-10+Cil group, signs of heart failure were si gnificantly attenuated despite only a modest reduction in systolic blood pr essure (-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 hyper trophy to failure.