Muscarinic and β-adrenergic regulation of heart rate, force of contraction and calcium current is preserved in mice lacking endothelial nitric oxide synthase
Muscarinic and β-adrenergic regulation of heart rate, force of contraction and calcium current is preserved in mice lacking endothelial nitric oxide synthase
复制标题
缺乏内皮一氧化氮合酶的小鼠中保留了对心率、收缩力和钙电流的毒蕈碱和β-肾上腺素能调节
DOI：
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
R. Fischmeister
中科院分区：
文献类型：
--
作者：
G. Vandecasteele;T. Eschenhagen;H. Scholz;B. Stein;I. Verde;R. Fischmeister
>一氧化氮（NO）是一种普遍存在的信号分子，由NO合酶（NOS）从L-精氨酸产生。在血管系统中，NO介导副交感神经内皮依赖性血管舒张。NO还可能介导心肌功能的副交感神经控制。这得到了以下观察结果的支持：NOS 3，内皮组成型NOS，在来自啮齿动物和人的正常心肌细胞中表达，NOS和/或鸟苷酸环化酶抑制剂拮抗毒蕈碱激动剂对心率、房室传导、收缩性和L型钙电流的作用。在这里，我们研究了基因工程小鼠的心脏的自主调节缺乏NOS 3（NOS 3-KO）（参考文献8）。我们发现，在从NOS 3-KO小鼠分离的心脏组织制备物中，对β-肾上腺素能和毒蕈碱激动剂的变时性和变力性反应没有改变，尽管这些小鼠对血管张力的副交感神经调节有缺陷。类似地，在来自NOS 3-KO小鼠和来自野生型小鼠的心肌细胞中，β-肾上腺素能刺激和钙电流的毒蕈碱抑制没有差异。RT-PCR未显示其他NOS亚型的上调。同样，Gi/Go蛋白和毒蕈碱受体密度不变。这些数据反驳了NOS 3对于心肌功能的正常自主控制是必需的这一观点。
>Nitric oxide (NO) is an ubiquitous signaling molecule produced from L-arginine by NO synthase (NOS). In the vasculature, NO mediates parasympathetic endothelium-dependent vasodilation. NO may also mediate the parasympathetic control of myocardial function. This is supported by the observations that NOS3, the endothelial constitutive NOS, is expressed in normal cardiac myocytes from rodents and human, and NOS and/or guanylyl cyclase inhibitors antagonize the effect of muscarinic agonists on heart rate, atrio–ventricular conduction, contractility and L-type calcium current. Here we examine the autonomic regulation of the heart in genetically engineered mice deficient in NOS3 (NOS3-KO)(ref. 8). We show that the chronotropic and inotropic responses to both β-adrenergic and muscarinic agonists were unaltered in isolated cardiac tissue preparations from NOS3-KO mice, although these mice have a defective parasympathetic regulation of vascular tone. Similarly, β-adrenergic stimulation and muscarinic inhibition of the calcium current did not differ in cardiac myocytes from NOS3-KO mice and those from wild-type mice. RT–PCR did not demonstrate upregulation of other NOS isoforms. Similarly, Gi/Go proteins and muscarinic receptor density were unaltered. These data refute the idea that NOS3 is obligatory for the normal autonomic control of cardiac muscle function.
DOI：
10.1073/pnas.95.11.6510
发表时间：
1998-05-26
影响因子：
11.1
作者：
Han, XQ;Kubota, I;Kelly, RA
通讯作者：
Kelly, RA
影响因子：
37.8
作者：
Hare, JM;Givertz, MM;Colucci, WS
通讯作者：
Colucci, WS
DOI：
10.1152/ajpcell.1996.271.1.c391
发表时间：
1996-07
期刊：
The American journal of physiology
影响因子：
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作者：
B. Wolska;M. Stojanovic;W. Luo;E. G. Kranias;R. Solaro
通讯作者：
B. Wolska;M. Stojanovic;W. Luo;E. G. Kranias;R. Solaro