title: Beneficial effect of candesartan on rat diastolic heart failure.
abstract: In this study, we examined whether an angiotensin II type 1 (AT1)-receptor blocker improves diastolic heart failure (DHF) in Dahl salt-sensitive (DS) rats. DHF was prepared by feeding DS rats on 8% NaCl diet from 7 weeks of age. DHF was estimated with echocardiography by measuring E velocity / A velocity (E/A) of left ventricular inflow. DS rats with established DHF were orally given candesartan (1 mg/kg per day) or vehicle. After 13 days of treatment, candesartan significantly improved DHF, as shown by the reduction of E/A from 4.49 +/- 1.04 to 1.98 +/- 0.54 (P<0.05) and prolonged survival rate more than the vehicle. Cardiac fibrosis, apoptosis, and gene expression were estimated by Sirius Red-staining, TUNEL-staining, and Northern blot analysis, respectively. The improvement of DHF by candesartan was accompanied by the decrease in cardiac hypertrophy, fibrosis, and apoptosis, and the reduction of gene expression of brain natriuretic peptide, collagen I, and monocyte chemoattractant protein-1. Moreover, candesartan decreased cardiac inflammatory cells and reactive oxygen species, estimated by counting ED-1-positive cells and the measurement of 4-hydroxy-2-nonenal staining, respectively. These results indicate that candesartan can improve diastolic dysfunction and may slow the progression of cardiac remodelling in DS rats with established DHF.
authors.affiliation: Department of Pharmacology, Osaka City University Graduate School of Medical Sciences, Osaka 545-8585, Japan.
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Wake
authors.forename: Shokei
authors.initials: S
authors.lastname: Kim-Mitsuyama
authors.forename: Yasukatsu
authors.initials: Y
authors.lastname: Izumi
authors.forename: Kaoru
authors.initials: K
authors.lastname: Yoshida
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Izumiya
authors.forename: Tokihito
authors.initials: T
authors.lastname: Yukimura
authors.forename: Masayuki
authors.initials: M
authors.lastname: Shiota
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshiyama
authors.forename: Junichi
authors.initials: J
authors.lastname: Yoshikawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwao
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D018932:Chemokine CCL2 / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D015150:Echocardiography, Doppler; D005355:Fibrosis / Q000188:drug therapy; D015870:Gene Expression / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D017382:Reactive Oxygen Species / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000009:adverse effects; D015996:Survival Rate; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D000447:Aldehydes; D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D018932:Chemokine CCL2; D024042:Collagen Type I; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D017673:Sodium Chloride, Dietary; D013777:Tetrazoles; D020097:Natriuretic Peptide, Brain; C027576:4-hydroxy-2-nonenal; C081643:candesartan