Abstract 3593: Angiotensin II Type1 Receptor Blocker Attenuates Myocardial NADPH Oxidase Activity in Advanced Stage of Hypertensive Diastolic Heart Failure
Background and Aim; Angiotensin II type 1 receptor antagonist (ARB) is increasingly prescribed for the treatment of heart failure with a growing body of clinical evidences. However, roles of ARB remain to be clarified in the treatment of diastolic heart failure (DHF), particularly at its advanced stage. This experimental study investigated the effects of ARB administered at an advanced stage of DHF.
Methods and Results: Dahl salt sensitive rats fed on 8% NaCl diet from age of 7 weeks represent overt DHF at age of 20 weeks as noted in our previous studies (hypertensive DHF model). The DHF model rats were randomly divided into 2 groups at age of 17 weeks when LV diastolic dysfunction, hypertrophy, fibrosis, macrophage infiltrations and reactive oxygen species (ROS) generation were already augmented; 6 rats treated for 3 weeks with a subdepressor dose of ARB (olmesartan 0.6mg/kg/day) and 6 untreated rats. The 3-week administration of ARB significantly decreased LV end-diastolic pressure and lung weight in association with the attenuation of LV hypertrophy, fibrosis and diastolic dysfunction. Macrophage infiltration was attenuated with decreased gene expression of transforming growth factor-β1 and monocyte chemoattractant protein-1 in the LV myocardium of the ARB-treated rats. The production of reactive oxygen species (ROS) was also decreased with NADPH oxidase activity.
Conclusions: ARB provides beneficial effects in DHF independent of its anti-hypertensive effects even if initiated at an advanced stage. The beneficial effects are at least partly attributed to the attenuation of inflammatory changes and ROS generation, and the decrease in NADPH oxidase activity may be responsible for the inhibition of oxidative stress.