FUNCTIONAL EVIDENCE THAT THE ANGIOTENSIN ANTAGONIST LOSARTAN CROSSES THE BLOOD-BRAIN-BARRIER IN THE RAT
FUNCTIONAL EVIDENCE THAT THE ANGIOTENSIN ANTAGONIST LOSARTAN CROSSES THE BLOOD-BRAIN-BARRIER IN THE RAT
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DOI：
10.1016/0361-9230(93)90036-b
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发表时间：
1993-01-01
影响因子：
3.8
通讯作者：
FERGUSON, AV
中科院分区：
文献类型：
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作者：
LI, ZH;BAINS, JS;FERGUSON, AV
氯沙坦是一种新型的血管紧张素（ANG） II亚型1 （AT1）受体的非肽能拮抗剂，可有效降低高肾素高血压大鼠的血压，阻断全身ANG II的升压反应。众所周知，在下丘脑室旁核（PVN）中存在高密度的ANG II受体。此外，起源于皮质下器官（SFO）的PVN的血管紧张能传入神经的激活可升高血压并促进PVN神经元的活动。我们在这里报道，全身给予氯沙坦（3mg /kg）可显著减弱SFO电刺激时的升压反应。静脉给药氯沙坦也能显著抑制PVN神经元对SFO刺激或局部压微注射ANG II的兴奋反应，分别在58.8%和88.9%的PVN细胞中得到抑制。这些药理作用是快速和可逆的，并伴有基本动脉血压或自发神经元活动的变化很小。这些观察结果表明全身性氯沙坦穿过血脑屏障（BBB）并作用于PVN内的AT1受体。
Losartan is a novel nonpeptidergic antagonist of angiotensin (ANG) II subtype 1 (AT1) receptors, which effectively lowers blood pressure in high-renin hypertensive rat and blocks the pressor response to systemic ANG II. It is well known that high densities of ANG II receptors exist in the hypothalamic paraventricular nucleus (PVN). In addition, activation of putative angiotensinergic afferents to the PVN originating in subfornical organ (SFO) elevates blood pressure and facilitates the activity of PVN neurons. We report here that systemic administration of losartan (3 mg/kg) significantly attenuates the pressor response to electrical stimulation of SFO. The excitatory responses of PVN neurons to SFO stimulation or local pressure microinjection of ANG II were also significantly inhibited in 58.8% and 88.9% of PVN cells, respectively, by intravenous administration of losartan. These pharmacological effects were rapid and reversible, and were accompanied by little change of basal arterial blood pressure or spontaneous neuronal activity. These observations suggest that systemic losartan crosses the blood-brain barrier (BBB) and acts at AT1 receptors within the PVN.