Therapic effects of CPU0213, a novel endothelin receptor antagonist, on isopreterenol induced cardiomyopathy

Abstract

Abstract: AIM: The present study was focused on the effects of isoproteronol induced cardiomyopathy, and the expression of sarcoplasm reticulum Ca2 + handlingprotein, sarco-endoplasmic reticulum ATPase 2a(SERCA2a). The therapeutic effects of CPU0213, a novel endothelin receptor antagonist were evaluated. METHODS: Male SD rats were administrated isoproterenol (2 mg·kg^-1 ·d^-1,s.c.) for 10 days. A subset of the rats were administrated CPU0213 (30mg·kg^-1 ·d^-1, s. c.) from d 6 to d 10.All the animals were subjected to cannulation through left carotid artery to measure LVSP, LVEDP, and±dp dtmax Expressions of SERCA2a were measured by reverse transcription polymerase chain reaction (RT-PCR) and western blotting assays. RESULTS: Isoproteronol caused a significant decline of SERCA2a expression in both mRNA and protein levels(P<0.05), in conjunction with decreased LVSP,±dp dt max, and elevated LVEDP(P<0.05). And CPU0213 recovered all these alterations partially. CONCLUSION: Blockade of endothelin receptors by CPU0213 is beneficial to isoproterenol caused impairment of cardiac function, in which process endothelin system probably mediates the adverse effects of excessive β-receptor activation.

Key words: isopreterenol, sarco-endoplasmic reticulum ATPase 2a(SERCA2a), endothelin receptor antagonist, CPU0213

CLC Number:

R965.2

TANG Xiao-yun, WANG Qiu-juan, DAI De-zai, DAI Yin. Therapic effects of CPU0213, a novel endothelin receptor antagonist, on isopreterenol induced cardiomyopathy[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(1): 36-41.

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