Beneficial effects of combination of ACE inhibitor and angiotensin II type 1 receptor blocker on cardiac remodeling in rat myocardial infarction.
OBJECTIVE
Angiotensin-converting enzyme (ACE) inhibitor and angiotensin II type I receptor blockers (ARB) prevent cardiac remodeling after myocardial infarction (MI). However, it is controversial whether combination therapy of ACE inhibitor and ARB is more effective on cardiac remodeling than each agent alone. In this study, we compared the effects of an ACE inhibitor (temocapril), an ARB (CS-866), and their combination on cardiac remodeling after MI.


METHODS
Temocapril at 3 or 30 mg/kg/day, CS-866 at 1 or 10 mg/kg/day, or combined temocapril and CS-866 at 1.5 and 0.5 mg/kg/day or at 15 and 5 mg/kg/day, respectively, were administered to rats after MI. At 4 weeks after MI, we assessed hemodynamics, cardiac function by Doppler echocardiography and non-infarcted myocardial mRNA expression.


RESULTS
Animals treated with a combination of the two drugs had hemodynamics, heart weights and dimensions similar to the other treated animals. However, the combination of the two drugs suppressed ANP, BNP and other gene expressions related to contractile proteins of fetal type and collagens more effectively than ACE inhibitor or ARB alone.


CONCLUSIONS
These data suggest that combination of the two drugs, independent of the hemodynamic effect, may improve left ventricular phenotypic change, collagen accumulation and diastolic function.
Nakamura
Yasuhiro
Y
Department of Internal Medicine and Cardiology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
Yoshiyama
Minoru
M
Omura
Takashi
T
Yoshida
Ken
K
Izumi
Yasukatsu
Y
Takeuchi
Kazuhide
K
Kim
Shokei
S
Iwao
Hiroshi
H
Yoshikawa
Junichi
J
D000804:Angiotensin II / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D015152:Blotting, Northern / Q000379:methods; D003094:Collagen / Q000235:genetics; D003971:Diastole; D004359:Drug Therapy, Combination; D015150:Echocardiography, Doppler; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D023421:Models, Animal; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000235:genetics; D000068557:Olmesartan Medoxomil; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000627:therapeutic use*; D013841:Thiazepines / Q000627:therapeutic use*; D020257:Ventricular Remodeling / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D012333:RNA, Messenger; D013777:Tetrazoles; D013841:Thiazepines; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D000068557:Olmesartan Medoxomil; D009320:Atrial Natriuretic Factor; C055603:temocapril hydrochloride; D003094:Collagen