Abstract 11962: Central Sympathoinhibition by Moxonidine Attenuated Brain Oxidative Stress, Prevented Cardiac Dysfunction and Improved Prognosis in Rats With Hypertensive Heart Failure
Background: In hypertensive heart failure (HHF), sympathetic hyperactivity worsens prognosis. The β-blocker treatment antagonizes sympathoexcitation at the peripheral and is an established therapeutic strategy for heart failure. However, the effect of central sympathoinhibition on HHF remains unclear. Therefore, we examined whether moxonidine, a central sympathoinhibitory agent acting on imidazoline-1 receptors (I1R) associated with oxidative stress in the rostral ventrolateral medulla (RVLM), has beneficial impact on HHF in rats.
Methods and Results: We fed Dahl salt-sensitive rats with high salt diet (HS) to create a model of HHF. This model represents a compensated left ventricular (LV) hypertrophic stage until 13 weeks of age with HS but begins to manifest heart failure after 14 weeks. We performed intracerebroventricular (ICV) infusion of moxonidine (Mox; n=17) or vehicle (Veh; n=28) from the beginning of heart failure phase to evaluate the effect of central sympathoinhibition. In comparison with Veh, Mox decreased urine norepinephrine (2.8±0.2 vs. 1.7±0.3 μg/day, p≤0.01) and heart rate (396±4 vs. 361±4 bpm, p≤0.001), improved survival (23 vs. 76 %, p≤0.05) as well as LV function (LVDd; 6.9±0.2 vs. 6.4±0.1 mm, p≤0.05, %FS; 38±1 vs. 45±1 %, p≤0.01, LVEDP; 14.2±2.7 vs. 7.3±1.7 mmHg, p≤0.05, LV -dP/dt; -7738±348 vs. -10394±1156 mmHg/s, p≤0.05) despite no significant differences in systolic blood pressure during ICV treatment. Moreover, Mox decreased LV interstitial and perivascular fibrosis, brain oxidative stress (Signal Decay Rate; 0.12±0.01 vs. 0.10±0.01 /min, p≤0.05), and increased the expression of I1R in the RVLM compared with Veh.
Conclusion: Moxonidine-induced central sympathoinhibition attenuated brain oxidative stress, prevented cardiac dysfunction and remodeling, and improved prognosis in rats with HHF. Central sympathoinhibition via I1R in the RVLM can be effective for the treatment of HHF.
- © 2013 by American Heart Association, Inc.