Angiotensin II type 1 receptor blocker attenuates diabetes-induced atrial structural remodeling.

Abstract

BACKGROUND:

Diabetes mellitus promotes atrial structural remodeling, thereby producing atrial arrhythmogenicity, where advanced glycation endproducts (AGEs) and their receptor (RAGE) are implicated to play a role in the pathogenesis.

PURPOSE:

We investigated the effects of candesartan, an angiotensin type II receptor blocker, on the diabetes-induced atrial structural change.

METHODS AND RESULTS:

Diabetes was induced in 8-week-old female Sprague-Dawley rats by intraperitoneal injection of streptozotocin at 70 mg/kg. Osmotic pumps were simultaneously set to infuse candesartan at a subdepressor dose of 0.05 mg/kg/day. Twelve weeks after the induction of diabetes, the blood glucose and glycated hemoglobin A1c were significantly higher in streptozotocin-injected rats than those in control rats, and were not affected by candesartan treatment. The atria of diabetic rats showed remarkable diffuse interstitial fibrosis with more enhanced protein expressions of RAGE and connective tissue growth factor (CTGF) compared with control ones. The treatment with candesartan significantly reduced CTGF expression and effectively suppressed the development of fibrotic deposition in diabetic animals.

CONCLUSIONS:

Candesartan reduced CTGF expression and attenuated the fibrosis in diabetic rat atria. These results implied the protective effects of candesartan on diabetes-related atrial arrhythmias.

• Authors: Takeshi Kato, Takeshi Yamashita, Akiko Sekiguchi, Takayuki Tsuneda, Kouichi Sagara, Masayuki Takamura, Shuichi Kaneko, Tadanori Aizawa, Long-Tai Fu
• Journal: Journal of cardiology (J Cardiol) Vol. 58 Issue 2 Pg. 131-6 (Sep 2011) ISSN: 1876-4738 [Electronic] Netherlands
• PMID: 21802905 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Benzimidazoles
• Biphenyl Compounds
• CCN2 protein, human
• Receptor for Advanced Glycation End Products
• Tetrazoles
• Connective Tissue Growth Factor
• candesartan

Topics

• Angiotensin II Type 1 Receptor Blockers (administration & dosage, pharmacology, therapeutic use)
• Animals
• Arrhythmias, Cardiac (prevention & control)
• Benzimidazoles (administration & dosage, pharmacology, therapeutic use)
• Biphenyl Compounds
• Connective Tissue Growth Factor (metabolism)
• Diabetes Mellitus, Experimental (drug therapy, pathology)
• Female
• Fibrosis
• Heart Atria (metabolism, pathology)
• Rats
• Rats, Sprague-Dawley
• Receptor for Advanced Glycation End Products (metabolism)
• Tetrazoles (administration & dosage, pharmacology, therapeutic use)