Nishimura Y, Xu T, Jöhren O, Häuser W, Saavedra J M
Section on Pharmacology, National Institute of Mental Health, Bethesda, MD 20892-1264, USA.
Basic Res Cardiol. 1998;93 Suppl 2:63-8. doi: 10.1007/s003950050221.
We studied cerebral blood flow autoregulation by laser Doppler flowmetry, and expression of brain angiotensin II AT1 receptors by quantitative autoradiography, after administration of an angiotensin AT1 receptor antagonist, CV-11974 (Candesartan, 0.5 or 1.0 mg/kg.day) for two weeks via subcutaneously implanted osmotic pumps in adult normotensive Wistar Kyoto and spontaneously hypertensive male rats (SHR). In SHR, the autoregulation curve was shifted towards higher blood pressures, when compared with that of normotensive Wistar Kyoto rats. Administration of CV-11974 shifted the autoregulation curve toward lower blood pressures in both Wistar Kyoto and SHR, partially normalizing the autoregulation curve in SHR. CV-11974 treatment markedly decreased the expression of AT1 receptors in Wistar Kyoto rats, both in areas outside the blood brain barrier (subfornical organ, 95% decrease) and inside the blood brain barrier (nucleus of the tractus solitarius, 87% decrease, and paraventricular nucleus, 96% decrease). Our results demonstrate that blockade of AT1 receptors tends to normalize the shift to higher pressures in the autoregulation curve of genetically hypertensive rats, and has a profound modulatory role in brain angiotensin II AT1 receptors.
我们通过激光多普勒血流测定法研究了脑血流自动调节，并通过定量放射自显影法研究了脑内血管紧张素II AT1受体的表达。在成年正常血压的Wistar Kyoto大鼠和自发性高血压雄性大鼠（SHR）中，通过皮下植入渗透泵给予血管紧张素AT1受体拮抗剂CV-11974（坎地沙坦，0.5或1.0mg/kg·天）两周。与正常血压的Wistar Kyoto大鼠相比，SHR的自动调节曲线向更高血压偏移。给予CV-11974可使Wistar Kyoto大鼠和SHR的自动调节曲线向更低血压偏移，部分使SHR的自动调节曲线正常化。CV-11974治疗显著降低了Wistar Kyoto大鼠血脑屏障外区域（穹窿下器官，降低95%）和血脑屏障内区域（孤束核，降低87%，室旁核，降低96%）的AT1受体表达。我们的结果表明，阻断AT1受体倾向于使遗传性高血压大鼠自动调节曲线向更高压力偏移正常化，并对脑内血管紧张素II AT1受体具有深远的调节作用。
