Chronic administration of moxonidine suppresses sympathetic activation in a rat heart failure model

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.