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 1 receptor agonist, on sympathetic activation and myocardial remodelling in a rat heart failure model. Rats were subjected to coronary artery ligation, and treated with moxonidine, 3 or 6 mg/kg/day, from 1 to 21 days after myocardial infarction. After 21 days, heart rate and blood pressure were measured in conscious, chronically instrumented rats. Plasma catecholamine levels were determined by high-performance liquid chromatography. Effects on post-myocardial infarction remodelling were evaluated from the ventricular weight body weight ratio and interstitial collagen deposition, measured morphometrically in the interventricular septum remote from the infarcted area. Moxonidine dose-dependently decreased myocardial infarction induced tachycardia but did not affect myocardial infarction reduced blood pressure. Plasma noradrenaline levels, which were elevated after myocardial infarction, decreased below sham-values with 6 mg/kg/day moxonidine. Ventricular weight–body weight ratio as well as interstitial collagen were significantly elevated in myocardial infarcted rats, and restored to sham values with 6 mg/kg/day moxonidine. These data suggest that moxonidine suppresses myocardial infarction induced sympathetic activation in a dose-dependent way as indicated by reduced heart rate and plasma noradrenaline levels. Furthermore, post-myocardial infarction remodelling may be attenuated at a higher dose-range of moxonidine as shown by normalisation of ventricular weight body weight ratio and interstitial collagen.