title: Effects of angiotensin-II receptor blocker candesartan cilexetil in rats with dilated cardiomyopathy.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata City, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Shirai
authors.forename: Kenichi
authors.initials: K
authors.lastname: Watanabe
authors.forename: Meilei
authors.initials: M
authors.lastname: Ma
authors.forename: Mir I I
authors.initials: MI
authors.lastname: Wahed
authors.forename: Mikio
authors.initials: M
authors.lastname: Inoue
authors.forename: Yuki
authors.initials: Y
authors.lastname: Saito
authors.forename: Palaniyandi Selvaraj
authors.initials: PS
authors.lastname: Suresh
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kashimura
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tachikawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Kodama
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Aizawa
mesh_terms: 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
chemical_list: 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