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: Ryotaro Wake, Shokei Kim-Mitsuyama, Yasukatsu Izumi, Kaoru Yoshida, Yasuhiro Izumiya, Tokihito Yukimura, Masayuki Shiota, Minoru Yoshiyama, Junichi Yoshikawa, Hiroshi Iwao
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 98 Issue 4 Pg. 372-9 (Aug 2005) ISSN: 1347-8613 [Print] Japan
• PMID: 16079469 (Publication Type: Journal Article)

Chemical References

• Aldehydes
• Angiotensin II Type 1 Receptor Blockers
• Benzimidazoles
• Biphenyl Compounds
• Chemokine CCL2
• Collagen Type I
• RNA, Messenger
• Reactive Oxygen Species
• Sodium Chloride, Dietary
• Tetrazoles
• Natriuretic Peptide, Brain
• 4-hydroxy-2-nonenal
• candesartan

Topics

• Aldehydes (metabolism)
• Angiotensin II Type 1 Receptor Blockers (pharmacology)
• Animals
• Apoptosis (drug effects)
• Benzimidazoles (pharmacology)
• Biphenyl Compounds
• Chemokine CCL2 (metabolism)
• Collagen Type I (metabolism)
• Echocardiography, Doppler
• Fibrosis (drug therapy)
• Gene Expression (drug effects)
• Heart Failure (drug therapy, etiology, metabolism, pathology)
• Immunohistochemistry
• Myocardium (metabolism, pathology)
• Natriuretic Peptide, Brain (metabolism)
• RNA, Messenger (metabolism)
• Rats
• Rats, Inbred Dahl
• Reactive Oxygen Species (metabolism)
• Sodium Chloride, Dietary (adverse effects)
• Survival Rate
• Tetrazoles (pharmacology)