Aging-related alterations in eNOS and nNOS responsiveness and smooth muscle reactivity of murine basilar arteries are modulated by apocynin and phosphorylation of myosin phosphatase targeting subunit-1
Aging-related alterations in eNOS and nNOS responsiveness and smooth muscle reactivity of murine basilar arteries are modulated by apocynin and phosphorylation of myosin phosphatase targeting subunit-1
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DOI：
10.1177/0271678x16649402
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发表时间：
2017-03-01
影响因子：
6.3
通讯作者：
Pfitzer, Gabriele
中科院分区：
文献类型：
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作者：
Lubomirov, Lubomir T.;Papadopoulos, Symeon;Pfitzer, Gabriele
衰老导致神经血管单元的所有组成部分发生重大变化，并损害脑供血。在这里，我们测试了衰老如何影响年轻（22个月；0 - ba）和老年（60 - 22个月）杂合MYPT1-T-696A/+敲入小鼠基底动脉的血管反应性。在等距安装的o-BA中，介质厚度增加了约10%，而被动长度张力关系没有改变。内皮剥蚀或抑制泛nos （100 μ mol/L L- name）可使y-BA和o-BA分别增加11%和23%的基底张力，而抑制nNOS （1 μ mol/L L- npa）可使两个年龄的基底张力均增加约10%。eNOS在o-BA中的表达量大约高出2倍。在o-BA中，u46619诱导力增强（pEC（50）约为6.9 vs pEC（50）约为6.5），而对DEA-NONOate、电场刺激或尼古丁的反应性降低。MLC20-S19和MYPT1-T-853的基础磷酸化在o-BA中较高，并被罗布麻素逆转。此外，渗透o-BA表现出增强的Ca2+敏感性。老的T-696A/+BA显示MYPT1-T696和MLC20磷酸化降低，L-NAME反应的基础音调降低，eNOS表达降低。结果表明，o-BA中的血管过度收缩是通过抑制MLCP介导的，并通过内皮细胞NO释放的上调部分补偿。
Aging causes major alterations of all components of the neurovascular unit and compromises brain blood supply. Here, we tested how aging affects vascular reactivity in basilar arteries from young (22months; o-BA) and old (>22months) heterozygous MYPT1-T-696A/+knock-in mice. In isometrically mounted o-BA, media thickness was increased by approximate to 10% while the passive length tension relations were not altered. Endothelial denudation or pan-NOS inhibition (100 mu mol/L L-NAME) increased the basal tone by 11% in y-BA and 23% in o-BA, while inhibition of nNOS (1 mu mol/L L-NPA) induced approximate to 10% increase in both ages. eNOS expression was approximate to 2-fold higher in o-BA. In o-BA, U46619-induced force was augmented (pEC(50) approximate to 6.9 vs. pEC(50) approximate to 6.5) while responsiveness to DEA-NONOate, electrical field stimulation or nicotine was decreased. Basal phosphorylation of MLC20-S19 and MYPT1-T-853 was higher in o-BA and was reversed by apocynin. Furthermore, permeabilized o-BA showed enhanced Ca2+-sensitivity. Old T-696A/+BA displayed a reduced phosphorylation of MYPT1-T696 and MLC20, a lower basal tone in response to L-NAME and a reduced eNOS expression. The results indicate that the vascular hypercontractility found in o-BA is mediated by inhibition of MLCP and is partially compensated by an upregulation of endothelial NO release.