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一氧化氮抑制AngⅡ介导的心肌肥大反应的信号机制

刘培庆, 鲁伟, 潘敬运

中山医科大学生理学教研室.广东,广州 510089

摘要

L-精氨酸(L-Arg)10、100#mu#mol/L分别增加心肌细胞NO水平16％及31％,L-Arg(100#mu#mol/L)还可增加心肌细胞eNOS mRNA表达,其作用可被NOS抑制剂L-NAME所抑制;L-Arg(100#mu#mol/L)可降低AngⅡ(0.1#mu#mol/L)诱导的心肌细胞ANP mRNA表达水平和蛋白合成速率,而在L-Arg处理之前用针对MKP-1的反义寡核苷酸转染心肌细胞,蛋白合成速率明显增加,可取消L-Arg的抑制作用,甚至超过AngⅡ组;L-Arg(100#mu#mol/L)明显增加MKP-1蛋白表达,比对照组增加225％,NOS抑制剂L-NAME及蛋白激酶G(PKG)抑制剂KT-5823皆可抑制L-Arg诱导的MKP-1蛋白表达,分别抑制88％、83％,而AngⅡ能增加L-Arg诱导的MKP-1的表达,较对照组增加365％,增强了L-Arg的作用。以上结果表明,NO抑制AngⅡ介导心肌肥大反应的机制可能是通过激活的PKG,促进MKP-1的表达,从而增加MAPK去磷酸化实现的。

关键词： 丝裂原活化蛋白激酶磷酸酶1; 蛋白激酶K; 心肌细胞; 肥大反应; 血管紧张素Ⅱ; 一氧化氮; 精氨酸

Molecular mechanism of nitric oxide in preventing cardiomyocytes from hypertrophic response induced by angiotensin Ⅱ

Liu Peiqing, Lu Wei, Pan Jingyun

Department of Physiology,Sun Yat-Sen University of Medical Sciences.Guangzhou 510089,Guangdong

Abstract

The results are as follows. (1) L-arginine (L-Arg) induced a dose-dependent increase in NO by 16% and 31% at the concentrations of 10 #mu#mol/L and 100 #mu#mol/L, respectively. L-Arg also increased the gene expression of eNOS. However, these effects were inhibited by L-NAME, the inhibitor of NOS. (2) The gene expression and the protein synthesis of ANP induced by Ang II (0.1 #mu#mol/L) were inhibited by L-Arg (100 #mu#mol/L). The inhibitory action of L-Arg was abolished after pretreatment with antisense oligoneucleotide against MKP-1. (3) L-Arg (100#mu#mol/L) increased the protein expression of MKP-1 by 225%, which was inhibited by L-NAME, an NOS inhibitor, and KT-5823, a cGMP-dependent protein kinase (PKG) inhibitor. However, Ang II enhanced the effect induced by L-Arg.

Key words: Mitogeiractivated protein kinase phosphatase-1;Cyclic GMP-dependent protein kinases;Cardiomyocyte;Hypertrophy;Angiotensin II;Nitric oxide;Arginine

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引用本文：

刘培庆, 鲁伟, 潘敬运. 一氧化氮抑制AngⅡ介导的心肌肥大反应的信号机制[J]. 生理学报 2002; 54 (3): .

Liu Peiqing, Lu Wei, Pan Jingyun. Molecular mechanism of nitric oxide in preventing cardiomyocytes from hypertrophic response induced by angiotensin Ⅱ. Acta Physiol Sin 2002; 54 (3): (in Chinese with English abstract).