Combined effects of enalapril and spironolactone in hamsters with dilated cardiomyopathy.
Chronic angiotensin I-converting enzyme inhibition can be associated with aldosterone escape. We investigated the effects of enalapril, spironolactone, and their combination on hemodynamics and cardiac remodeling in cardiomyopathic hamsters to determine whether these drugs could exert additive effects. Cardiomyopathic hamsters, Bio TO-2 dilated strain, were orally treated with enalapril (20 mg. kg. day ) and/or spironolactone (20 mg. kg. day ) according to a 2 x 2 factorial design from 120 days of age. Animals were investigated at 180 (10 animals per group) and 240 (16 animals per group) days of age. Compared with corresponding untreated groups, enalapril significantly decreased mean blood pressure (-18%); enalapril and spironolactone significantly increased cardiac output (+28%, +11%) and femoral blood flow (+10%, +12%) and significantly decreased systemic (-38%, -17%) and femoral (-26%, -13%) vascular resistances. Enalapril and spironolactone significantly decreased left ventricle cavity area (-21%, -26%) and left (-34%, -47%) and right (-37%, -48%) ventricle collagen density. Spironolactone significantly increased left ventricle wall thickness (+4%). There were significant enalapril x spironolactone interactions for most variables (compared with control group, +52%, +36%, +45% for cardiac output; +26%, +28%, +26% for femoral blood flow; -50%, -30%, -45% for systemic vascular resistance; -33%, -20%, -35% for femoral vascular resistance; -27%, -31%, -40% for left ventricle cavity area; and -46%, -58%, -60% for left and -39%, -50%, -66% for right ventricle collagen density in enalapril, spironolactone, and enalapril + spironolactone groups, respectively). In cardiomyopathic hamsters, enalapril and spironolactone in combination did not improve hemodynamics more than enalapril alone but induced stronger effects than each drug alone on cardiac remodeling.
Goineau
Sonia
S
Laboratoire de Pharmacologie Expérimentale et Clinique, UPRES EA 3194 Groupe de Recherche Cardio-Vasculaire, Faculté de Médecine, Hôpital de Pontchaillou, Rennes, France.
Pape
Danielle
D
Guillo
Pascal
P
Ramée
Marie-Paule
MP
Bellissant
Eric
E
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy*; D006224:Cricetinae; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000494:pharmacology* / Q000627:therapeutic use; D006439:Hemodynamics / Q000187:drug effects*; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D009929:Organ Size / Q000187:drug effects; D013148:Spironolactone / Q000494:pharmacology* / Q000627:therapeutic use; D020257:Ventricular Remodeling / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D004656:Enalapril