Chronic peripheral administration of the angiotensin II AT(1) receptor antagonist candesartan blocks brain AT(1) receptors.
Chronic peripheral administration of the angiotensin II AT(1) receptor antagonist candesartan blocks brain AT(1) receptors.
复制标题
血管紧张素 II AT(1) 受体拮抗剂坎地沙坦的长期外周给药可阻断脑 AT(1) 受体。
DOI：
10.1016/s0006-8993(00)02377-5
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发表时间：
2000
期刊：
影响因子：
2.9
通讯作者：
Saavedra,JM
中科院分区：
文献类型：
--
作者：
Nishimura,Y;Ito,T;Hoe,K;Saavedra,JM
脑血管紧张素II通过刺激脑AT 1受体，调节垂体激素和自主神经活动。我们给药了难以克服的AT 1拮抗剂坎地沙坦，s.c.通过渗透压微泵持续14天，以确定外周慢性AT 1阻断是否影响脑中AT 1受体结合和mRNA。坎地沙坦（0.1、0.5或1.0 mg/kg/天）外周给药可抑制肾上腺肾小球和肾小球中的AT 1结合。此外，坎地沙坦剂量依赖性地降低血脑屏障外（穹窿下器官和最后区）和内（下丘脑室旁核和孤束核）脑区的AT 1结合。相反，坎地沙坦外周给药不影响AT 1A受体mRNA（这些区域表达的主要受体亚型）或血管紧张素II与蓝斑或下橄榄核中AT 2受体的结合。我们的研究结果表明，慢性外周治疗与选择性，有效的AT 1受体拮抗剂不仅抑制外周，但也脑AT 1受体。这些中枢效应可能在AT 1拮抗剂坎地沙坦的降压作用中发挥作用。
Brain Angiotensin II, through stimulation of brain AT1receptors, regulates pituitary hormones and autonomic activity. We have administered the insurmountable AT1antagonist Candesartan, s.c. via osmotic minipumps for 14 days, to determine whether peripheral chronic AT1blockade affects AT1receptor binding and mRNA in the brain. Peripherally administered Candesartan (0.1, 0.5 or 1.0 mg/kg per day) inhibits AT1binding in adrenal gland zona glomerulosa and kidney glomeruli. In addition, Candesartan dose-dependently decreases AT1binding in brain areas outside (subfornical organ and area postrema) and inside (paraventricular nucleus of the hypothalamus and nucleus of the solitary tract) the blood–brain barrier. Conversely, peripheral treatment with Candesartan does not affect AT1Areceptor mRNA, the predominant receptor subtype expressed in these areas, or Angiotensin II binding to AT2receptors in the locus coeruleus or inferior olive. Our results demonstrate that chronic peripheral treatment with selective, potent AT1antagonists not only inhibits peripheral but also brain AT1receptors. These central effects may play a role in the antihypertensive effects of the AT1antagonist Candesartan.