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

• Published in: European journal of pharmacology 2000-05, Vol.397 (1), p.113-120
• Main Authors: Van Kerckhoven, Roeland, van Veen, Toon A.B, Boomsma, Frans, Saxena, Pramod R, Schoemaker, Regien G
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blood Pressure - drug effects; Cardiomegaly - pathology; Cardiomegaly - prevention & control; Cardiotonic agents; Cardiovascular system; Catecholamines - blood; Collagen; Collagen - drug effects; Collagen - metabolism; Disease Models, Animal; Dose-Response Relationship, Drug; Heart failure; Heart Failure - etiology; Heart Failure - physiopathology; Heart Failure - prevention & control; Heart Rate - drug effects; Heart Ventricles - drug effects; Heart Ventricles - metabolism; Heart Ventricles - pathology; Hypertrophy; Imidazoles - pharmacology; Male; Medical sciences; Moxonidine; Myocardial Infarction - complications; Pharmacology. Drug treatments; Rat; Rats; Rats, Wistar; Sympathetic activation; Sympathetic Nervous System - drug effects; Sympathetic Nervous System - physiopathology
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(00)00232-6

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.