摘要
培养的家兔胸主动脉血管平滑肌细胞(VSMC)分别以内皮素(ET-1)、一氧化氮(NO)前体L-Arg和NO供体SIN-1刺激,或用ET-1+L-Arg、ET-1+SIN-1联合刺激,测VSMC3H-TdR掺入、丝裂素活化蛋白激酶(MAPK)活性及蛋白激酶C(PKC)活性的改变,以研究NO抑制ET-1促VSMC增殖作用的信号转导途径。结果表明:(1)ET-110-8mol/L单独刺激,3H-TdR掺入、MAPK活性、PKC活性分别较对照组增加5倍、4倍和3倍(P<0.01);L-Arg或SIN-1刺激对上述指标无明显影响;(2)ET-1与L-Arg(2、5、10nmol/L)联合刺激,3H-TdR掺入、MAPK活性和PKC活性均明显低于ET-1单独刺激组;(3)ET-1与SIN-1(5、10、50μmol/L)联合刺激,3H-TdR掺入、MAPK活性和PKC活性也均明显低于ET-1单独刺激组。结果提示:NO抑制ET-1促VSMC增殖的作用,此作用与NO抑制ET-1激活PKC、MAPK活性终止ET-1的细胞内信号转导途径有关。
The signal transduction pathways of the inhibitory effect of nitric oxide (NO) on endothelin (ET)-induced proliferation of vascular smooth muscle cells (VSMCs) were studied.3H-thymidine(TdR) incorporation, mitogen-activated protein kinase (MAPK)activity and protein kinase C (PKC) activity of cultured VSMCs of rabbits thoracic aorta were measured in the presence of either NO precursor L-arginine (L-Arg) or NO donor 3 morpholino sydnonimine-hydrochloride (SIN-1), or ET-1 alone or with L-Arg or SIN-1.The results show: (1) ET-1 (10-8 mol/L) significantly increased VSMCs 3H-TdR incorporation (5 times, P <0.01), MAPK activity (4 times, P < 0.01) and PKC activity (3 times, P <0.01 ), as compared with control. L-Arg or SIN-1 alone was without effect on 3H-TdR incorporation, MAPK activity and PKC activity. (2) When ET1 and L-Arg (2, 5, 10 mmol/L) were simultaneously administered, 3H-TdR incorporation and activity of both MAPK and PKC were all significantly dacreased in comparison with the ET group. (3) When ET-1 + SIN-1 (5, 10, 50μmol/L), the effects coincide with those of the ET1-1+ L-Arg groups. These findings indicate that NO inhibition of the signal transduction pathways of the ET-1-induced proliferation of VSMCs may be mediated by the inhibition of ET-1-induced activation of both PKC and MAPK.
出处
《生理学报》
CAS
CSCD
北大核心
1998年第4期379-384,共6页
Acta Physiologica Sinica
关键词
一氧化氮
内皮素
血管平滑肌细胞
细胞增殖
nitric oxide
endothelin
mitogen-activated protein kinase
protein kinase C
vascular smooth muscle cell