Enalapril and losartan are more effective than carvedilol in preventing dilated cardiomyopathy in the Syrian cardiomyopathic hamster.
To assess the role of the renin-angiotensin (RAS) and adrenergic systems in the development and progression of dilated cardiomyopathy in the Syrian cardiomyopathic hamster (SCH), echocardiographic parameters were evaluated in 6-month-old animals after 5 months of treatment with enalapril (25 mg/kg/day) plus losartan (10 mg/kg/day), or with carvedilol (1 mg/kg/day). Cardiac output indexes (COI) increased by 53% after RAS blockade and by 20% after beta-blockade in SCH. Moreover, LVEDV and LVESV decreased 30% and 62%, respectively (P < .05) during RAS blockade, whereas ejection fraction (EF) increased by 48%. By contrast, carvedilol reduced LVESV by only 28% (P < .05) and increased EF by only 15% (P < .05). These results suggest that RAS activation plays a critical role in the development of cardiac dysfunction in SCH and that suppression of RAS may be more effective than beta-blockade in retarding the development of cardiomyopathy in SCH. Owing to timing (pre-heart failure stage) and to the single dose protocol, the implications of this study for human subjects remain to be clarified.
Crespo
Maria J
MJ
Department of Physiology, University of Puerto Rico School of Medicine, San Juan, PR 009365067. mcrespo@rcm.upr.edu
Cruz
Nildris
N
Altieri
Pablo I
PI
Escobales
Nelson
N
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D002311:Cardiomyopathy, Dilated / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000517:prevention & control*; D000077261:Carvedilol; D006224:Cricetinae; D004195:Disease Models, Animal; D018450:Disease Progression; D004656:Enalapril / Q000494:pharmacology*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D008647:Mesocricetus; D011412:Propanolamines / Q000494:pharmacology*; D012084:Renin-Angiotensin System / Q000187:drug effects; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D014463:Ultrasonography; D016277:Ventricular Function, Left / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D004656:Enalapril; D019808:Losartan