Effects of angiotensin-II receptor blocker candesartan cilexetil in rats with dilated cardiomyopathy.
We examined effects of an angiotensin-II receptor blockers, candesartan cilexetil, in rats with dilated cardiomyopathy after autoimmune myocarditis. Candesartan cilexetil showed angiotensin-II blocking action in a dose-dependent manner in rats with dilated cardiomyopathy. Twenty-eight days after immunization, surviving Lewis rats were divided into four groups and given candesartan cilexetil at 0.05 mg/kg, 0.5 mg/kg or 5 mg/kg per day (Group-C0.05, n = 15, Group-C0.5, n = 15 and Group-C5, n = 15, respectively) or vehicle alone (Group-V, n = 15). After oral administration for 1 month, the left ventricular end-diastolic pressure and heart weight/body weight ratio were lower in Group-C0.05 (13.3+/-1.1 mmHg and 3.7+/-0.2 g/kg, respectively), in Group-C0.5 (8.0+/-0.9 mmHg and 3.3+/-0.1 g/kg, respectively) and in Group-C5 (5.5+/-1 mmHg and 3.1+/-0.1 g/kg, respectively) than in Group-V (13.5+/-1.0 mmHg and 3.8+/-0.2 g/kg, respectively). The area of myocardial fibrosis was also lower in Group-C0.05 (25+/-3%), in Group-C0.5 (20+/-3%), and in Group-C5 (12+/-1%) than in Group-V (32+/-4%). Furthermore, expressions of transforming growth factor-beta1 and collagen-III mRNA were suppressed in Group-C0.05 (349+/-23% and 395+/-22%, respectively), Group-C0.5 (292+/-81% and 364+/-42%, respectively) and in Group-C5 (204+/-63% and 259+/-33%, respectively) compared with those in Group-V (367+/-26% and 437+/-18%, respectively). These results suggest that candesartan cilexetil can improve the function of inefficient heart.
Shirai
Ken
K
Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata City, Japan.
Watanabe
Kenichi
K
Ma
Meilei
M
Wahed
Mir I I
MI
Inoue
Mikio
M
Saito
Yuki
Y
Suresh
Palaniyandi Selvaraj
PS
Kashimura
Takeshi
T
Tachikawa
Hitoshi
H
Kodama
Makoto
M
Aizawa
Yoshifusa
Y
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001327:Autoimmune Diseases / Q000150:complications; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D008297:Male; D009205:Myocarditis / Q000150:complications; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D015854:Up-Regulation / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D002316:Cardiotonic Agents; D024061:Collagen Type III; D012333:RNA, Messenger; D013777:Tetrazoles; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000804:Angiotensin II; C077793:candesartan cilexetil