R. Van Kerckhoven et al., Chronic administration of moxonidine suppresses sympathetic activation in a rat heart failure model, EUR J PHARM, 397(1), 2000, pp. 113-120
Excessive sympathetic activity contributes to cardiovascular abnormalities,
which negatively affect the prognosis of heart failure. The present study
evaluated the effects of moxonidine, an imidazoline I, receptor agonist, on
sympathetic activation and myocardial remodelling in a rat heart failure m
odel. Rats were subjected to coronary artery Ligation, and treated with mox
onidine, 3 or 6 mg/kg/day, from 1 to 21 days after myocardial infarction. A
fter 21 days, heart rate and blood pressure were measured in conscious, chr
onically instrumented rats. Plasma catecholamine levels were determined by
high-performance liquid chromatography. Effects on post-myocardial infarcti
on remodelling were evaluated from the ventricular weight body weight ratio
and interstitial collagen deposition, measured morphometrically in the int
erventricular septum remote from the infarcted area. Moxonidine dose-depend
ently decreased myocardial infarction induced tachycardia but did not affec
t myocardial infarction reduced blood pressure. Plasma noradrenaline levels
, which were elevated after myocardial infarction, decreased below sham-val
ues with 6 mg/kg/day moxonidine. Ventricular weight-body weight ratio as we
ll as interstitial collagen were significantly elevated in myocardial infar
cted rats, and restored to sham values with 6 mg/kg/day moxonidine. These d
ata suggest that moxonidine suppresses myocardial infarction induced sympat
hetic activation in a dose-dependent way as indicated by reduced heart rate
and plasma noradrenaline levels. Furthermore, post-myocardial infarction r
emodelling may be attenuated at a higher dose-range of moxonidine as shown
by normalisation of ventricular weight body weight ratio and interstitial c
ollagen. (C) 2000 Elsevier Science B.V. All rights reserved.