Li Z, Bains J S, Ferguson A V
Department of Physiology, Queen's University, Kingston, Ontario, Canada.
Brain Res Bull. 1993;30(1-2):33-9. doi: 10.1016/0361-9230(93)90036-b.
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.
氯沙坦是一种新型的非肽类血管紧张素（ANG）II 1型（AT1）受体拮抗剂，它能有效降低高肾素型高血压大鼠的血压，并阻断对全身性ANG II的升压反应。众所周知，下丘脑室旁核（PVN）中存在高密度的ANG II受体。此外，源自穹窿下器（SFO）的假定的向PVN的血管紧张素能传入神经的激活会升高血压并促进PVN神经元的活动。我们在此报告，全身性给予氯沙坦（3 mg/kg）可显著减弱对SFO电刺激的升压反应。静脉注射氯沙坦后，PVN神经元对SFO刺激或局部压力微量注射ANG II的兴奋性反应也分别在58.8%和88.9%的PVN细胞中受到显著抑制。这些药理作用迅速且可逆，并且基础动脉血压或自发神经元活动几乎没有变化。这些观察结果表明，全身性氯沙坦可穿过血脑屏障（BBB）并作用于PVN内的AT1受体。
