Combined angiotensin II AT1-receptor blockade and angiotensin I-converting enzyme inhibition on survival and cardiac remodeling in chronic heart failure in rats.
BACKGROUND
Angiotensin I-converting enzyme inhibition (ACEI) and angiotensin II AT(1)-receptor blockade are effective at improving survival and limiting cardiac remodeling in the rat model of postischemic heart failure. Whether their combination yields additive/synergistic effects is unknown.


RESULTS
Rats underwent coronary artery ligation and 7 days later were treated orally for 9 months with placebo (controls), 5 mg/kg valsartan, 1 mg/kg enalapril (doses submaximally effective at reducing mortality in the experimental model used), or 5 mg/kg valsartan and 1 mg/kg enalapril combined. Compared with controls, valsartan, enalapril, and their combination decreased mortality by 40% (P =.006), 21% (P =.065), and 33% (P =.032), respectively, but there was no significant difference between the 3 treatments. At the doses used, valsartan, but neither enalapril nor the combination, slightly limited cardiac hypertrophy and fibrosis development and reduced left ventricular end-diastolic pressure as assessed in the surviving animals at 9 months.


CONCLUSIONS
In experimental chronic heart failure in rats, valsartan reduces mortality similar to other AT(1)-receptor blockers and a combination of AT(1)-receptor blockade (valsartan) and ACEI (enalapril) at submaximal doses does not exert additive/synergistic beneficial effects on mortality.
Richer
C
C
Département de Pharmacologie, Faculté de Médecine Paris-Sud, 63 rue Gabriel Péri, 94276 Le Kremlin-Bicêtre Cedex, France.
Fornes
P
P
Domergue
V
V
De Gasparo
M
M
Giudicelli
J F
JF
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004656:Enalapril / Q000008:administration & dosage / Q000494:pharmacology*; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D000068756:Valsartan
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D013777:Tetrazoles; D004656:Enalapril; D000068756:Valsartan; D014633:Valine