The mechanism of ET-1 induced growth-promoting effect in cardiac myocytesChinese Full Text

ZHU Xiao-xing~(1),MEI Qi-bing~(1),LIU Li~(1),LU Shun-yan~(2),HU Yu-zhen~(2),ZHANG Feng~(1),CHEN Ding-zhang~(3),PEI Zhao-hui~(2),YUAN Wen-jun~(4)(1.Department of Pharmacology,Faculty of Pharmacology;2.Department of Physiology,Faculty of(Preclinical) Medicine;3.Department of Ultrasound,Xijing Hospital,Fourth Military Medical University,(Xi′an),Shaanxi 710032;4.Department of Physiology,Faculty of Preclinical Medicine,Second Military Medical University,Shanghai 200003,China)

Abstract: AIM: To investigate the mechanism of cardiac myocyte hypertrophy induced by endothelin-1（ET-1）.METHODS: ET-1 has been known to be a potent stimulator for neonatal rat ventricular myocyte（NRVM） hypertrophy in vitro.Chronic ET-1 stimulation produces increased cell size and protein synthesis.Over the past several years,cultured NRVM have been used to delineate the signaling pathways activated by ET-1.We studied the influence of protein synthesis stimulated by chronic ET-1 using the blockers of L-type calcium channel（larcidipine and MN9202）,the inhibitor of calcium activated chlorine channel（niflumic acid,NFA）,the inhibitor of protein kinase C（PKC）（chelerythrine,che） and the inhibitor of ERK（PD98059,PD）.RESULTS: Intracellular protein contents in cardiac myocytes in each groups were: ET-1,312±30 μg/ml（14% higher than control,P＜0.05）;ET-1+NFA,280±10 μg/ml（10% lower than ET-1,P＜0.05）;ET-1+che,283±10 μg/ml（9% lower than ET-1,P＜0.05）;ET-1+MN9202,285±27 μg/ml（8.6% lower than ET-1,P＞0.05）;ET-1+Larcidipine,275±22 μg/ml（13.1% lower than ET-1,P＜0.05）;ET-1+PD98059,293±33 μg/ml（6.1% lower than ET-1,P＞0.05）.CONCLUSION: ET-1 induced growth-promoting in myocytes is associated with L-type calcium channels and calcium activated chlorine channels.PKC and ERK may be important intracellular signaling transduction pathways in ET-1-induced cardiac hypertrophy in cultured neonatal rat cardiac myocytes.

Keywords：

endothelin-1; L-type calcium channel; calcium activated chlorine channel; protein kinase C; extracellular-signal regulated kinase;

DOI：
10.13191/j.chj.2005.05.41.zhuxx.012
Series：
Subject：
Classification Code：
R541

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