蛋白激酶C在血管紧张素Ⅱ抑制心肌细胞一氧化氮合成中的作用  

Effect of protein kinase C on inhibition of nitric oxide synthesis in cultured neonatal rat cardiomyocytes by angiotensinⅡ

作　　者：符史干[1] 刘培庆[1] 鲁伟[1] 龚素珍[1] 潘敬运[1] 

机构地区：[1]中山医科大学生理教研室,广州510080

出　　处：《生理学报》2000年第4期318-322,共5页Acta Physiologica Sinica

基　　金：SupportedbytheChineseMedicalBoard (America) (No 93 5 94)andNaturalScienceFoundationofGuangdong (No 96 0 12 4)

摘　　要：实验用硝酸还原酶法测定培养新生大鼠心肌细胞亚硝酸盐 (NO 2 )和硝酸盐 (NO 3)总量 (NO 2 /NO 3) ,反映心肌细胞一氧化氮 (NO)生成情况 ,观察血管紧张素Ⅱ (AngⅡ )对心肌细胞NO生成的影响及其蛋白激酶C (PKC)在该效应中的作用。结果显示 :AngⅡ可减少心肌细胞NO的含量 ,并具有明显的剂量 效应关系 ;AngⅡ受体拮抗剂saralasin可明显抑制AngⅡ对NO生成的影响 ;L 精氨酸 (L Arg)明显增加心肌细胞NO的浓度 ,此效应可被一氧化氮合酶 (NOS)抑制剂L NAME所抑制 ,L Arg未能消除AngⅡ抑制NO的作用 ;用佛波酯 (PMA)处理心肌细胞 ,其NO的生成明显减少 ,L NAME可加强此抑制效应 ;PKC抑制剂staurosporine (Stau)可明显削弱AngⅡ抑制心肌细胞NO生成的效应。结果提示 :AngⅡ具有抑制心肌细胞NO生成的作用 ,此作用可能是通过抑制心肌细胞NOS的活性而实现的 ;AngⅡ受体介导AngⅡ抑制心肌细胞NO生成的作用 ;激活PKC可使新生大鼠心肌细胞NO生成减少 ,NOS参与此抑制效应 ,新生大鼠心肌细胞NO生成过程的信号转导通路可能与PKC有关 ;PKC参与AngⅡ抑制心肌细胞NO的生成。The purpose of the present study was to investigate the effect of angiotensinⅡ (AngⅡ) on nitric oxide (NO) concentration and its signal transduction pathway in cultured neonatal rat cardioymocytes. NO content was measured in cultured neonatal rat cardiomyoctes using a nitrite/nitrate colormetric method kit. NO content was represented by measured nitrite (NO 2) and nitrate (NO 3) level (NO 2/NO 3). The results are as follows. NO production was decreased by Ang Ⅱ in a dose dependent manner but increased by L Arg. The Saralasin, an antagonist of AngⅡ receptor, inhibited the effect of AngⅡ on NO production. The effect of AngⅡ on NO production was inhibited by NOS blocker N G nitro L arginine methyl ester (L NAME) but not by L Arg. Pretreatment of Phorbol 12 myristate 13 acetate (PMA), a PKC activator, decreased NO concentration significantly. This effect was strengthened by L NAME. Staurosporine, a PKC inhibitor, abolished the inhibiting effect of AngⅡ on production of NO. The above results suggest that AngⅡ could decrease NO content in cultured neonatal rat cardiomyocytes significantly. Activity of NOS may be inhibited by AngⅡ. AngⅡ receptor was involved in the inhibitory effect of AngⅡ on NO production. Activation of protein kinase C (PKC) decreased significantly NO production in cultured neonatal rat cardiomyoctes, which appears to be associated with PKC in the signal transduction pathway.

关 键 词：心肌细胞培养 血管紧张素Ⅱ 一氧化氮 蛋白激酶C 

分 类 号：R331[医药卫生—人体生理学]