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首页> 外文期刊>American Journal of Physiology >Differential expression of angiotensin II type 1 receptor subtypes within the cerebral microvasculature
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Differential expression of angiotensin II type 1 receptor subtypes within the cerebral microvasculature

机译：血管紧张素II型1受体亚型在脑微血管内的差异表达

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Arteries and arterioles constrict in response to intraluminal pressure to generate myogenic tone, but the molecular nature of the vascular force-sensing mechanism is not fully characterized. Here, we investigated the role of angiotensin II type 1 receptors (AT1Rs) on vascular smooth muscle cells in the development of myogenic tone in cerebral parenchymal arterioles from mice. We found that pretreatment with the AT1R blocker losartan inhibited the development of myogenic tone in these vessels but did not alter the luminal diameter of arterioles with preestablished tone. Rodents express two AT1R isotypes: AT1Ra and AT1Rb. We previously demonstrated that AT1Rb is expressed at much higher levels compared with AT1Ra in cerebral pial arteries and is required for myogenic contractility in these vessels, whereas AT1Ra is unnecessary for this function. Here, we found that AT1Ra and AT1Rb are expressed at similar levels in parenchymal arterioles and that genetic knockout of AT1Ra blunted the ability of these vessels to generate myogenic tone. We also found that AT1Rb and total AT1R expression levels are much lower in parenchymal arterioles compared with pial arteries and that parenchymal arterioles are less sensitive to the vasoconstrictive effects of the endogenous AT1R ligand angiotensin II (ANG II). We conclude that 1) AT1Rs are critical for the initiation, but not the maintenance, of myogenic tone in parenchymal arterioles, and 2) lower levels of AT1Rb and total AT1R in parenchymal arterioles compared with pial arteries result in differences in myogenic and ANG II-induced vasoconstriction between these vascular segments.NEW & NOTEWORTHY Myogenic tone is critical for appropriate regulation of cerebral blood flow, but the mechanisms used by vascular smooth muscle cells to detect changes in intraluminal pressure are not fully characterized. Here, we demonstrate angiotensin II receptor type 1 (AT1R) is indispensable to initiation, but not maintenance, of myogenic tone in cerebral parenchymal arterioles. Furthermore, we demonstrate differences in AT1R expression levels lead to critical differences in contractile regulation between parenchymal arterioles and cerebral pial arteries.
机译：动脉和动脉瘤响应于腔内压力产生糜源性调，但血管力传感机制的分子性质没有完全表征。在这里，我们研究了血管紧张素II型受体（AT1RS）对血管平滑肌细胞的作用，以在小鼠脑实质动脉瘤中发育中的肌原子炎。我们发现与AT1R阻滞剂氯沙坦的预处理抑制了这些血管中的肌原型调的发展，但没有改变动脉源的腔直径，具有预ablim的基调。啮齿动物表达两个AT1R同种型：AT1RA和AT1RB。我们以前证明，与脑小术中的AT1RA相比，AT1RB表达得多，并且在这些血管中的肌遗传性收缩性需要，而AT1RA是不必要的。在这里，我们发现AT1RA和AT1RB在实质动脉中的类似水平表达，并且AT1RA的遗传敲除钝化了这些血管产生糜源性调的能力。我们还发现，与小型动脉相比，在实质动脉比较的情况下，at1RB和总AT1R表达水平低得多，并且实质的动脉杆菌对内源性AT1R配体血管紧张素II（ANG II）的血管收缩效应敏感。我们得出结论，1）AT1RS对于发起，但不维持的肌遗传调节，2）与小型动脉相比，实质动脉中的较低水平的AT1RB和总AT1R，导致肌源性和ANG II-的差异这些血管段之间的血管收缩.New和值得注意的糜源性对于适当调节脑血流量至关重要，但血管平滑肌细胞使用的机制来检测腔内压力变化的特征。在这里，我们证明了血管紧张素II受体1（AT1R）是脑实质动脉瘤中的肌遗传学术中的引发，但不维持的是不可或缺的。此外，我们证明了AT1R表达水平的差异导致实质动脉和脑小脉之间的收缩调节的临界差异。

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