کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2534369 | 1559086 | 2009 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Telmisartan, an angiotensin II type 1 receptor antagonist, attenuates T-type Ca2+ channel expression in neonatal rat cardiomyocytes Telmisartan, an angiotensin II type 1 receptor antagonist, attenuates T-type Ca2+ channel expression in neonatal rat cardiomyocytes](/preview/png/2534369.png)
Recently, it has been revealed that angiotensin II type 1 receptor (AT1) antagonists act as antiarrhythmic agents and that the T-type Ca2+ channel plays an important role in arrhythmia. However, it remains unclear how the T-type Ca2+ channel expression system is involved in angiotensin II-mediated arrhythmogenesis in cardiomyocytes. In this study, we investigated the effect of telmisartan, an AT1 receptor antagonist, on transcriptional regulation of T-type Ca2+ channel isoform (Cav3.1 and Cav3.2) expression and cardiac contractility using rat neonatal cardiomyocytes. Cultured cardiomyocytes were stimulated with telmisartan and/or angiotensin II for 24 h. T-type Ca2+ currents (ICa.T) were then measured with the patch clamp technique, while Cav3.1 and Cav3.2 mRNA expression were assessed by real-time PCR. Expression of Cav3.1 and Cav3.2 mRNA as well as ICa.T current density in cardiomyocytes increased significantly after long-term application of angiotensin II (24 h), which was accompanied by extracellular signal-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) phosphorylation. In contrast, telmisartan decreased Cav3.1 and Cav3.2 mRNA expression as well as ICa.T in a dose-dependent manner in the absence of angiotensin II. In addition, the basal phosphorylation level of p38MAPK but not ERK1/2 was decreased by telmisartan in the absence of angiotensin II. Valsartan, an AT1 receptor antagonist, did not mimic the action of telmisartan, while the action of telmisartan was completely blocked by valsartan. These results indicate that telmisartan attenuates T-type Ca2+ channel expression likely through p38MAPK activity in an agonist-independent manner, which suggests a novel pharmacological action of telmisartan.
Journal: European Journal of Pharmacology - Volume 609, Issues 1–3, 1 May 2009, Pages 105–112