氯沙坦和卡托普利对压力超负荷大鼠心脏β-肌球蛋白重链基因表达的抑制作用

Inhibition of beta-myosin heavy chain gene expression in pressure overload rat heart by losartan and captopril.

作者信息

Ling Q, Chen T H, Guo Z G

机构信息

Laboratory of Molecular Pharmacology, Hunan Medical University, Changsha, China.

出版信息

Zhongguo Yao Li Xue Bao. 1997 Jan;18(1):63-6.

PMID:10072897

Abstract

AIM

To study the effects of losartan and captopril on beta-myosin heavy chain (MHC), and alpha-MHC gene expression.

METHODS

Pressure overload was produced by abdominal aortic coarctation (AAC) in rats. alpha- and beta-MHC mRNA were measured by Northern blot.

RESULTS

In left ventricular myocardium of sham-operated rats, the alpha-MHC mRNA predominated, while the beta-MHC mRNA was only detectable. In response AAC, there was a 70-fold increase in the beta-MHC mRNA (P < 0.01), while alpha-MHC mRNA reduced to 26% (P < 0.01). Losartan (3 mg.kg-1.d-1, i.g. for 11 d) to AAC rats caused inhibitions of beta-MHC by 96% and alpha-MHC by 86% gene expression without lowering blood pressure. A reduction in beta-MHC mRNA was also seen in captopril-treated rats (30 mg.kg-1.d-1, i.g. for 11 d), but the inhibitory effect of captopril on alpha-MHC mRNA was less than that of losartan (44% vs 86%, P < 0.05).

CONCLUSIONS

The shift of MHC isoform induced by pressure overload is due to up-regulation of beta-MHC and down-regulation of alpha-MHC gene expression. Inhibition of beta-MHC gene expression by losartan is achieved primarily by direct blockade of angiotensin II type I receptors in the myocardium, independent on hemodynamics.

摘要

目的

研究氯沙坦和卡托普利对β-肌球蛋白重链（MHC）及α-MHC基因表达的影响。

方法

通过腹主动脉缩窄（AAC）建立大鼠压力超负荷模型。采用Northern印迹法检测α-和β-MHC mRNA。

结果

假手术大鼠左心室心肌中，α-MHC mRNA占主导，而β-MHC mRNA仅可检测到。对AAC的反应中，β-MHC mRNA增加了70倍（P<0.01），而α-MHC mRNA降至26%（P<0.01）。给予AAC大鼠氯沙坦（3mg·kg-1·d-1，灌胃11天）可使β-MHC基因表达抑制96%，α-MHC基因表达抑制86%，且不降低血压。卡托普利治疗的大鼠（30mg·kg-1·d-1，灌胃11天）也可见β-MHC mRNA减少，但卡托普利对α-MHC mRNA的抑制作用小于氯沙坦（44%对86%，P<0.05）。