AIM: To study the roles and mechanisms of ERKs and intracellular free calcium in cardiomyocyte hypertrophic response induced by endothelin-1(ET-1). METHODS: (1) Neonatal rat cardiomyocyte hypertrophic response was assayed by measuring cell surface area and protein content; (2) ERKs activity was determined by Whatman Paper Filter method; (3) Intracellular free calcium concentration (［Ca2+］i) was measured using Fura-2/AM as a fluorescent indicator. RESULTS: (1) ET-1 could increase total protein production, surface area, ERKs activity and ［Ca2+］i in cultured cardiomyocyte in dose-dependent manner at concentrations ranging from 10-9 to 10-7 mol/L. And this effect could be abolished by BQ123, an antagonist of ETA receptor, partly inhibited by PTX, but not by BQ788, an antagonist of ETB receptor.（2）The activation of ERKs and the increase of ［Ca2+］i induced by ET-1 were obviously inhibited by PD98059, a selective ERKs kinase inhibitor, and nifedipine, a calcium channel blocker, respectively. Both antagonists partially inhibited ET-1-stimulated cardiomyocyte hypertrophic response. (3) Staurosporine, a selective PKC inhibitor, could inhibit ET-1-stimulated cardiomyocyte hypertrophic response and increase of ［Ca2+］i, but not affect the activation of ERKs. CONCLUSION: Cardiomyocyte hypertrophic response induced by ET-1 is mediated by ETA receptor coupled to PTX-sensitive G-protein, which involves at least two signalling pathways: PKC-mediated increase of ［Ca2+］i , and PKC-independent activation of ERKs.%目的：研究细胞外信号调节激酶（ERKs）及细胞内游离钙（［Ca2+］i）在内皮素-1（ET-1）介导心肌细胞肥大反应中的作用及机制。方法：利用培养的新生大鼠心肌细胞，①以蛋白合成速率、蛋白含量及细胞表面积为心肌肥大反应的指标；②用滤纸法测定ERKs活性；③用Fura-2/AM作为钙荧光指示剂测定心肌［Ca2+］i浓度。结果: ①ET-1浓度依赖性增加新生大鼠心肌细胞蛋白质含量和心肌细胞表面积、ERKs活性及［Ca2+］i浓度，以上作用可被ETA受体拮抗剂BQ123所完全抑制，被百日咳毒素（PTX）部分抑制，而ETB受体拮抗剂BQ788则无效；②ERKs激酶特异性抑制剂PD98059可完全抑制ET-1激活ERKs的作用，钙通道拮抗剂硝苯地平可明显抑制ET-1介导的［Ca2+］i浓度增加，但二者皆仅部分抑制ET-1介导的心肌细胞肥大反应；③蛋白激酶C（PKC）选择性抑制剂staurosporine并不能明显抑制ET-1介导的ERKs激活，但可抑制ET-1介导的的［Ca2+］i浓度增加及心肌细胞肥大反应。结论：ET-1主要通过ETA受体并经PTX敏感的G-蛋白介导心肌细胞肥大反应，该作用至少涉及两条途径：①通过PKC介导的心肌［Ca2+］i浓度增加；②不通过 PKC介导的ERKs激活。
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