Rosiglitazone induces arrhythmogenesis in diabetic hypertensive rats with calcium handling alteration

Ting I. Lee, Yao Chang Chen, Yu Hsun Kao, Fone Ching Hsiao, Yung Kuo Lin, Yi Jen Chen

研究成果: 雜誌貢獻文章同行評審

22 引文 斯高帕斯(Scopus)

摘要

Background: Diabetes and hypertension have significant effects on cardiac calcium (Ca2+) regulation, which plays an essential role in determining cardiac function. The effect of peroxisome proliferator-activated receptor (PPAR)-γ agonists on Ca2+ regulation in the cardiomyocytes is unclear. Objective: The purpose of this study was to investigate the effects of hypertension, diabetes, and PPAR-γ agonist-rosiglitazone on the regulation of Ca2+ and the electrophysiological characteristics of isolated ventricular myocytes. Methods: The indo-1 fluorometric ratio technique and whole-cell patch clamp were used to investigate intracellular Ca2+ (Ca2+i), action potentials, and ionic currents in ventricular myocytes from rats of Wistar-Kyoto (WKY), diabetic WKY (induced by streptozotocin), diabetic WKY treated with rosiglitazone (5 mg/kg), spontaneously hypertensive rats (SHR), diabetic SHR, and diabetic SHR treated with rosiglitazone. Western blot was used to evaluate protein expressions of sarcoplasmic reticulum ATPase (SERCA2a), Na +-Ca2+ exchanger (NCX), and ryanodine receptor (RyR). Results: Diabetic WKY and diabetic SHR had smaller sarcoplasmic reticulum Ca2+ contents, and Ca2+i transients with a prolonged decay portion, down-regulated SERCA2a, NCX, and RyR protein expressions and smaller L-type Ca2+ currents than non-diabetic WKY and SHR, respectively. The Ca2+ dysregulations in diabetes were attenuated in rats treated with rosiglitazone. Diabetes and hypertension both prolonged the action potential duration which were enhanced by the use of rosiglitazone, and induced the genesis of triggered activity. Conclusions: Diabetes and hypertension modulate Ca2+ handling. Rosiglitazone significantly changed the Ca2+ regulation and electrophysiological characteristics, and may contain an arrhythmogenic potential in diabetes with hypertension.
原文英語
頁(從 - 到)299-307
頁數9
期刊International Journal of Cardiology
165
發行號2
DOIs
出版狀態已發佈 - 五月 10 2013

ASJC Scopus subject areas

  • 心臟病學與心血管醫學

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