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.
Van Kerckhoven
R
R
Department of Pharmacology, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR, Rotterdam, Netherlands. vankerckhoven@farma.fgg.eur.nl
van Veen
T A
TA
Boomsma
F
F
Saxena
P R
PR
Schoemaker
R G
RG
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000473:pathology / Q000517:prevention & control; D002395:Catecholamines / Q000097:blood; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009203:Myocardial Infarction / Q000150:complications; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology
D002395:Catecholamines; D007093:Imidazoles; D003094:Collagen; C043482:moxonidine