The brain renin-angiotensin system contributes to the hypertension in mice containing both the human renin and human angiotensinogen transgenes
The brain renin-angiotensin system contributes to the hypertension in mice containing both the human renin and human angiotensinogen transgenes
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DOI：
10.1161/01.res.83.10.1047
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发表时间：
1998-11-16
影响因子：
20.1
通讯作者：
Sigmund, CD
中科院分区：
文献类型：
--
作者：
Davisson, RL;Yang, GY;Sigmund, CD
我们以前已经表明，小鼠转基因的人肾素和人血管紧张素原基因（RA+）表现出适当的组织和细胞特异性表达的两个转基因，有4倍高的血浆血管紧张素II（AII）水平，是慢性高血压。然而，循环和组织来源的AII在这些动物中引起高血压的相对贡献尚不清楚。我们假设，脑肾素-血管紧张素系统有助于在这个模型中的血压升高。为了解决这一假设，平均动脉压（MAP）和心率在清醒的，不受约束的小鼠后，他们与脑室内插管和颈动脉和颈静脉导管的仪器测量。侧脑室注射选择性A Ⅱ 1型受体拮抗剂氯沙坦（10 μ g，1 μ L）在RA+小鼠中引起的MAP峰值下降显著大于非转基因RA-对照小鼠（-29+/-4对-4+/-2 mm Hg，P0.05），而AVPX导致RAS小鼠的MAP下降显著大于RA-小鼠（-24+/-2对-6+/-1，P
We have previously shown that mice transgenic for both the human renin and human angiotensinogen genes (RA+) exhibit appropriate tissue- and cell-specific expression of both transgenes, have 4-fold higher plasma angiotensin II (AII) levels, and are chronically hypertensive. However, the relative contribution of circulating and tissue-derived AII in causing hypertension in these animals is not known. We hypothesized that the brain renin-angiotensin system contributes to the elevated blood pressure in this model. To address this hypothesis, mean arterial pressure (MAP) and heart rate were measured in conscious, unrestrained mice after they were instrumented with intracerebroventricular cannulae and carotid arterial and jugular vein catheters. Intracerebroventricular administration of the selective AII type 1 (AT-1) receptor antagonist losartan (10 mu g, 1 mu L) caused a significantly greater peak fall in MAP in RA+ mice than in nontransgenic RA- controls (-29+/-4 versus -4+/-2 mm Hg, P0.05), whereas AVPX caused a significantly greater fall in MAP in RAS compared with RA- mice (-24+/-2 versus -6+/-1, P