Central sympathoinhibition by moxonidine attenuates brain oxidative stress, prevents cardiac remodeling and improves prognosis associated with reduction of sympathetic hyperactivity in rats with hypertensive heart failure

Abstract

BackgroundHypertension causes hypertensive heart failure (HHF). In HHF, excessive sympathoexcitation leads to poor prognosis. However, the effect of central sympathoinhibition on survival in HHF remains unclear. Therefore, we examined whether moxonidine, a sympathoinhibitory agent acting on nischarin associated with oxidative stress, improves prognosis in a rat model of HHF and has antioxidant effects in the brain.Methods and ResultsWe fed Dahl salt‐sensitive (DS) rats with high salt diet (HS) to create a model of HHF. This model represents a compensated left ventricular (LV) hypertrophic stage, subsequently a HF stage. We used DS rats with HS as HHF and performed intracerebroventricular infusion of moxonidine or vehicle to evaluate the effect of central sympathoinhibition. In comparison with vehicle, moxonidine decreased urine norepinephrine (2.8±0.2 vs. 1.7±0.3 μg/day, p<0.01), 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). Moreover, moxonidine decreased LV fibrosis and brain oxidative stress (Signal Decay Rate; 0.12±0.01 vs. 0.10±0.01/min, p<0.05).ConclusionMoxonidine‐induced central sympathoinhibition attenuates brain oxidative stress, prevents cardiac remodeling and improves prognosis in rats with HHF.