cGMP-dependent protein kinase I mediates the negative inotropic effect of cGMP in the murine myocardium
cGMP-dependent protein kinase I mediates the negative inotropic effect of cGMP in the murine myocardium
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DOI：
10.1161/hh0102.103222
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发表时间：
2002-01-11
影响因子：
20.1
通讯作者：
Feil, R
中科院分区：
文献类型：
--
作者：
Wegener, JW;Nawrath, H;Feil, R
为了研究cGMP依赖性蛋白激酶I（cGKI）对心脏收缩性的作用，在来自野生型（WT）小鼠和来自常规和条件性cGKI敲除小鼠的电驱动心肌中研究收缩力（F-c）。8-Br-cGMP和8-pCPT-cGMP均减少幼年WT心肌中的Fc，但不减少幼年cGKI无效突变体中的Fc。类似地，cGMP类似物降低了WT小鼠的毛喉素刺激的心室肌中的F-c，但没有降低cGKI无效突变体的F-c。相比之下，卡巴胆碱降低了两组动物的F-c。8-Br-cGMP也降低了成年WT小鼠心肌中的F-c，但未降低成年心肌细胞特异性cGKI敲除小鼠的F-c。这些结果表明，cGKI介导cGMP在幼年和成年小鼠心肌中的负性肌力作用。
To study the role of cGMP-dependent protein kinase I (cGKI) for cardiac contractility, force of contraction (F-c) was studied in electrically driven heart muscle from wild-type (WT) mice and from conventional and conditional cGKI knockout mice. Both 8-Br-cGMP and 8-pCPT-cGMP reduced Fc in cardiac muscle from juvenile WT but not from juvenile cGKI-null mutants. Similarly, the cGMP analogues reduced F-c in forskolin-stimulated ventricular muscle from WT mice but not from cGKI-null mutants. In contrast, carbachol reduced F-c in both groups of animals. 8-Br-cGMP reduced F-c also in heart muscle from adult WT mice but not from adult cardiomyocyte-specific cGKI-knockout mice. These results demonstrate that cGKI mediates the negative inotropic effect of cGMP in the myocardium of juvenile and adult mice.