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

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)299-307
Number of pages9
JournalInternational Journal of Cardiology
Volume165
Issue number2
DOIs
Publication statusPublished - May 10 2013

Keywords

  • Calcium handling
  • Cardiomyocytes
  • Diabetes mellitus
  • Hypertension

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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