Central sympathoinhibition improves left ventricular function and survival during the transition from hypertrophy to heart failure in Dahl salt‐sensitive rats

Abstract

BackgroundSympathetic hyperactivity is cardinal manifestation in heart failure (HF). Enhanced central sympathetic drive leads to poor prognosis in HF. Moxonidine is a sympathoinhibitory antihypertensive drug acting on the imidazoline receptors in the central nervous system. Therefore, we hypothesized that moxonidine improves hypertension induced cardiac remodeling, function, and survival in Dahl‐salt sensitive hypertensive rats.Methods and ResultsDahl salt‐sensitive rats fed 8% NaCl diet from age 7 weeks served as hypertension‐induced HF and followed until 20 week‐old. Salt loading increases blood pressure, left ventricle hypertrophy, and progressive urinary norepinephrine excretion (uNE). Fractional shortening (%FS) was gradually reduced overtime. Intracerebroventricular infusion of moxonidine or vehicle was performed from 14 to 20 week‐old. Moxonidine tended to lower heart rate and blood pressure. Moxonidine attenuated the reduction of %FS (37±1.3 vs. 43±0.9%, n=7, n=4, p<0.05) and lowered uNE (3.0±0.2 vs. 0.6±0.2μg/day, n=7, n=4, p<0.001). Furthermore, moxonidine improved the survival rate (50 vs. 80%, 20 week‐old, n=10, n=5 p<0.05).ConclusionMoxonidine acting on the central nervous system improves the cardiac function and prognosis in this rats model of hypertension associated with sympathoinhibition.