Circulating angiotensin II gains access to the hypothalamus and brain stem during hypertension via breakdown of the blood-brain barrier.
Circulating angiotensin II gains access to the hypothalamus and brain stem during hypertension via breakdown of the blood-brain barrier.
复制标题
高血压期间，循环血管紧张素 II 通过破坏血脑屏障进入下丘脑和脑干。
DOI：
10.1161/hypertensionaha.113.01743
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发表时间：
2014-03
期刊：
影响因子：
--
通讯作者：
Stern JE
中科院分区：
文献类型：
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作者：
Biancardi VC;Son SJ;Ahmadi S;Filosa JA;Stern JE
血管紧张素ii介导的血管性脑炎症是神经源性高血压的一种新的病理生理机制。然而，高血压患者血脑屏障完整性和中枢血管紧张素II介导神经体液激活的确切潜在机制和功能后果尚不清楚。在这里，我们的目的是确定参与神经体液调节的下丘脑和脑干关键区域的血脑屏障通透性是否在高血压期间发生改变。通过血管内注射荧光染料和免疫组织化学后的数字成像量化，我们发现在自发性高血压大鼠的下丘脑室旁核、孤立束核和延髓吻侧的血脑屏障通透性增加，以及关键的血脑屏障蛋白成分改变，这些都是已知在高血压期间促进神经体液激活的关键脑区。使用AT1受体拮抗剂氯沙坦可防止自发性高血压大鼠血脑屏障破坏，包括渗透性增加和组成蛋白下调，但使用直接血管扩张剂肼嗪则不能。重要的是，我们发现循环血管紧张素II外溢到这些大脑区域，与神经元和小胶质细胞共定位。综上所述，我们的研究揭示了高血压期间血管紧张素II介导的一种新的前驱机制，通过这种机制，循环血管紧张素II引起血脑屏障通透性增加，进而促进其进入已知参与血压调节的关键脑区域。
Angiotensin II-mediated vascular brain inflammation emerged as a novel pathophysiological mechanism in neurogenic hypertension. However, the precise underlying mechanisms and functional consequences in relation to blood brain barrier integrity and central angiotensin II actions mediating neurohumoral activation in hypertension are poorly understood. Here, we aimed to determine whether blood brain barrier permeability within critical hypothalamic and brainstem regions involved in neurohumoral regulation was altered during hypertension. Using digital imaging quantification following intravascularly injected fluorescent dyes and immunohistochemistry, we found increased blood brain barrier permeability, along with altered key blood brain barrier protein constituents, in spontaneously hypertensive rats within the hypothalamic paraventricular nucleus, the nucleus of the solitary tract, and the rostral ventrolateral medulla, all critical brain regions known to contribute to neurohumoral activation during hypertension. Blood brain barrier disruption, including increased permeability and down-regulation of constituent proteins, was prevented in spontaneously hypertensive rats treated with the AT1 receptor antagonist Losartan, but not with hydralazine, a direct vasodilator. Importantly, we found circulating angiotensin II to extravasate into these brain regions, co-localizing with neurons and microglial cells. Taken together, our studies reveal a novel angiotensin II-mediated feed-forward mechanism during hypertension, by which circulating angiotensin II evokes increased blood brain barrier permeability, facilitating in turn its access to critical brain regions known to participate in blood pressure regulation.