Nifedipine enhances the cardioprotective effect of an angiotensin-II receptor blocker in an experimental animal model of heart failure.
This study was designed to examine the hypothesis that a calcium channel blocker nifedipine (CCB) could enhance the cardioprotective effect of an angiotensin-ll receptor blocker candesartan (ARB) in the treatment for heart failure. Isoproterenol (ISP) was injected into male rats at 300 mg/kg to produce progressive heart failure. Three months later, the rats were divided into 4 groups and treated for 4 weeks with 1) vehicle (n = 20), 2) ARB at 0.2 mg/kg/day (n = 6), 3) CCB at 10 mg/kg/day (n = 6), or 4) both drugs (n = 8). Rats injected with saline served as controls (n = 13). ISP caused severe myocardial degeneration and decreased the capillary density (D(cap)) of the left ventricular (LV) myocardium (mean +/- SD: 2,197 +/- 627 vs. 2,847 +/- 298 N/mm2 for normal controls), while increasing plasma thiobarbituric acid-reactive substances (TBARS; 3.6 +/- 1.1 vs. 1.9 +/- 0.5 nmol/ml). Although ARB therapy preserved cardiac morphology, it had little effect on D(cap) or oxidative stress. On the other hand, CCB decreased plasma TBARS and 4-hydroxy-2-nonenal protein expression in LV myocardium. Furthermore, the combination of CCB and ARB increased D(cap) and preserved the ultrastructure of LV myocardium, so this combination may be a useful option for the treatment of heart failure.
Okuda
Nobuaki
N
Third Department of Medicine, Osaka Medical College, Takatsuki, Japan.
Hayashi
Tetsuya
T
Mori
Tatsuhiko
T
Inamoto
Sakiko
S
Okabe
Makoto
M
Mieno
Shigetoshi
S
Horimoto
Hitoshi
H
Kitaura
Yasushi
Y
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D001835:Body Weight; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002196:Capillaries; D002316:Cardiotonic Agents / Q000494:pharmacology; D003326:Coronary Circulation; D004195:Disease Models, Animal; D004357:Drug Synergism; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006973:Hypertension / Q000150:complications / Q000188:drug therapy; D008297:Male; D008854:Microscopy, Electron; D009206:Myocardium / Q000473:pathology / Q000648:ultrastructure; D009543:Nifedipine / Q000494:pharmacology*; D009929:Organ Size; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D017725:Ventricular Pressure
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D002121:Calcium Channel Blockers; D002316:Cardiotonic Agents; D013777:Tetrazoles; D017392:Thiobarbituric Acid Reactive Substances; D009543:Nifedipine; C081643:candesartan