Cellular and molecular alterations in the beta adrenergic system with cardiomyopathy induced by tachycardia.
Cellular and molecular alterations in the beta adrenergic system with cardiomyopathy induced by tachycardia.
复制标题
心动过速诱发心肌病时β肾上腺素能系统的细胞和分子改变。
DOI：
10.1093/cvr/28.8.1243
复制
发表时间：
1994
影响因子：
10.8
通讯作者：
Zile,MR
中科院分区：
文献类型：
--
作者：
Spinale,FG;Tempel,GE;Mukherjee,R;Eble,DM;Brown,R;Vacchiano,CA;Zile,MR
目的：目的：探讨心肌细胞功能的变化与心动过速诱发的心肌病中 β 肾上腺素能系统成分的蛋白质和 mRNA 含量变化之间的关系。方法：测量对照猪 (n = 6) 和接受三周起搏诱发室上性心动过速的猪 (n = 6) 的离体心肌细胞的收缩功能和 β 肾上腺素能反应性。从肌膜制剂中测定β受体密度和亲和力、G蛋白复合物的刺激性（Gs）和抑制性（Gi）亚基的相对含量以及腺苷酸环化酶活性。为了确定这些变化是否伴随着β肾上腺素能系统特定成分的稳态mRNA水平的改变，测量了β1肾上腺素能受体和G蛋白复合物的Gαs和Gαi2亚基的mRNA含量。 结果：与对照组相比，慢性室上性心动过速导致左心室舒张末期尺寸增加36％，左心室缩短分数减少61％。患有心动过速性心肌病的心脏的心肌细胞的孤立心肌细胞缩短速度比对照心肌细胞低 50%。在 50 nM 异丙肾上腺素或 2 μM 毛喉素存在下，肌病肌细胞的心肌细胞缩短速度比对照组低 65%。随着心动过速性心肌病的发展，与对照相比，β肾上腺素能受体密度下降25%，亲和力无变化，Gs下降35%，Gi增加50%以上。与对照组相比，室上性心动过速患者的基础腺苷酸环化酶活性以及异丙肾上腺素和毛喉素刺激的腺苷酸环化酶活性下降了 50% 以上。随着心动过速心肌病的发展，Gαi2mRNA的相对含量增加了三倍，与对照相比，β、受体或Gαs的mRNA相对丰度没有变化。结论：随着心动过速心肌病的发展，心肌细胞β肾上腺素能反应性的变化是由于细胞机制的改变（β受体和Gs密度减少，Gi增加）和分子机制的改变（GimRNA增加）心血管研究1994；28：1243-1250
Objective:The aim was to examine the relationship between changes in myocyte function to changes in protein and mRNA content of components of the β adrenergic system with tachycardia induced cardiomyopathy.Methods:Contractile function and β adrenergic responsiveness were measured in isolated myocytes from control pigs (n = 6) and in pigs subjected to three weeks of pacing induced supraventricular tachycardia (n = 6). β Receptor density and affinity, the relative content of the stimulatory (Gs) and inhibitory (Gi) subunits of the G protein complex, and adenylate cyclase activity were determined from sarcolemmal preparations. In order to determine whether these changes were accompanied by alterations in steady state mRNA levels for specific components of the β adrenergic system, mRNA content for β1the adrenergic receptor and the Gαsand Gαi2subunits of the G protein complex was measured.Results:Chronic supraventricular tachycardia caused a 36% increase in left ventricular end diastolic dimension and a 61% decrease in left ventricular fractional shortening compared to controls. The velocity of isolated myocyte shortening was 50% lower in myocytes from hearts with tachycardic cardiomyopathy than in control myocytes. In the presence of 50 nM isoprenaline or 2 μM forskolin, the velocity of myocyte shortening was 65% lower in the myopathic myocytes than in the controls. With the development of tachycardic cardiomyopathy, β adrenergic receptor density fell by 25% with no change in affinity, Gsdecreased by 35%, and Giincreased by over 50% compared to controls. Basal adenylate cyclase activity and isoprenaline and forskolin stimulated adenylate cyclase activity fell by over 50% with supraventricular tachycardia compared to controls. The relative content of Gαi2mRNA increased threefold with the development of tachycardic cardiomyopathy with no change in the relative abundance of mRNA for the β, receptor or Gαswhen compared with controls.Conclusions:The changes in myocyte β adrenergic responsiveness with the development of tachycardic cardiomyopathy are due to alterations in cellular mechanisms (decreased β receptor and Gsdensity, increased Gi) and in molecular mechanisms (increased GimRNA content).Cardiovascular Research1994;28:1243-1250