Moxonidine-induced central sympathoinhibition improves prognosis in rats with hypertensive heart failure.

Abstract

OBJECTIVES:

Enhanced central sympathetic outflow is an indicator of the prognosis of heart failure. Although the central sympatholytic drug moxonidine is an established therapeutic strategy for hypertension, its benefits for hypertensive heart failure are poorly understood. In the present study, we investigated the effects of central sympathoinhibition by intracerebral infusion of moxonidine on survival in a rat model of hypertensive heart failure and the possible mechanisms involved.

METHODS AND RESULTS:

As a model of hypertensive heart failure, we fed Dahl salt-sensitive rats an 8% NaCl diet from 7 weeks of age. Intracerebroventricular (ICV) infusion of moxonidine (moxonidine-ICV-treated group [Mox-ICV]) or vehicle (vehicle-ICV-treated group [Veh-ICV]) was performed at 14-20 weeks of age, during the increased heart failure phase. Survival rates were examined, and sympathetic activity, left ventricular function and remodelling, and brain oxidative stress were measured. Hypertension and left ventricular hypertrophy were established by 13 weeks of age. At around 20 weeks of age, Veh-ICV rats exhibited overt heart failure concomitant with increased urinary norepinephrine (uNE) excretion as an index of sympathetic activity, dilated left ventricle, decreased percentage fractional shortening, and myocardial fibrosis. Survival rates at 21 weeks of age (n = 28) were only 23% in Veh-ICV rats, and 76% (n = 17) in Mox-ICV rats with concomitant decreases in uNE, myocardial fibrosis, collagen type I/III ratio, brain oxidative stress, and suppressed left ventricular dysfunction.

CONCLUSION:

Moxonidine-induced central sympathoinhibition attenuated brain oxidative stress, prevented cardiac dysfunction and remodelling, and improved the prognosis in rats with hypertensive heart failure. Central sympathoinhibition can be effective for the treatment of hypertensive heart failure.

• Authors: Nobuhiro Honda, Yoshitaka Hirooka, Koji Ito, Ryuichi Matsukawa, Keisuke Shinohara, Takuya Kishi, Keiji Yasukawa, Hideo Utsumi, Kenji Sunagawa
• Journal: Journal of hypertension (J Hypertens) Vol. 31 Issue 11 Pg. 2300-8; discussion 2308 (Nov 2013) ISSN: 1473-5598 [Electronic] England
• PMID: 24096260 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antihypertensive Agents
• Imidazoles
• moxonidine

Topics

• Animals
• Antihypertensive Agents (pharmacology)
• Heart Failure (drug therapy, etiology, mortality, physiopathology)
• Hypertension (complications, drug therapy)
• Hypertrophy, Left Ventricular (etiology)
• Imidazoles (pharmacology)
• Infusions, Intraventricular
• Male
• Prognosis
• Rats
• Rats, Inbred Dahl
• Ventricular Dysfunction, Left (drug therapy, etiology, physiopathology)
• Ventricular Function, Left (drug effects)