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 language | English |
|---|---|
| Pages (from-to) | 299-307 |
| Number of pages | 9 |
| Journal | International Journal of Cardiology |
| Volume | 165 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - May 10 2013 |
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Keywords
- Calcium handling
- Cardiomyocytes
- Diabetes mellitus
- Hypertension
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
Cite this
Rosiglitazone induces arrhythmogenesis in diabetic hypertensive rats with calcium handling alteration. / Lee, Ting I.; Chen, Yao Chang; Kao, Yu Hsun; Hsiao, Fone Ching; Lin, Yung Kuo; Chen, Yi Jen.
In: International Journal of Cardiology, Vol. 165, No. 2, 10.05.2013, p. 299-307.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Rosiglitazone induces arrhythmogenesis in diabetic hypertensive rats with calcium handling alteration
AU - Lee, Ting I.
AU - Chen, Yao Chang
AU - Kao, Yu Hsun
AU - Hsiao, Fone Ching
AU - Lin, Yung Kuo
AU - Chen, Yi Jen
PY - 2013/5/10
Y1 - 2013/5/10
N2 - 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.
AB - 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.
KW - Calcium handling
KW - Cardiomyocytes
KW - Diabetes mellitus
KW - Hypertension
UR - http://www.scopus.com/inward/record.url?scp=84876684394&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84876684394&partnerID=8YFLogxK
U2 - 10.1016/j.ijcard.2011.08.072
DO - 10.1016/j.ijcard.2011.08.072
M3 - Article
C2 - 21917327
AN - SCOPUS:84876684394
VL - 165
SP - 299
EP - 307
JO - International Journal of Cardiology
JF - International Journal of Cardiology
SN - 0167-5273
IS - 2
ER -