Effects of intracerebroventricular losartan on angiotensin II-mediated pressor responses and c-fos expression in near-term ovine fetus
Effects of intracerebroventricular losartan on angiotensin II-mediated pressor responses and c-fos expression in near-term ovine fetus
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DOI：
10.1002/cne.20802
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发表时间：
2005-12-26
影响因子：
2.5
通讯作者：
Xu, Z
中科院分区：
文献类型：
--
作者：
Shi, LJ;Mao, CP;Xu, Z
肾素-血管紧张素系统在心血管控制中发挥着重要作用。脑室内 (i.c.v.) 血管紧张素 (ANG) II 在 90% 妊娠的胎儿中引起可靠的升压反应。为了确定大脑 AT(1) 和 AT(2) 受体在这种反应中的作用，在长期准备的近足绵羊胎儿中研究了中枢 AT(1) 和 AT(2) 受体拮抗剂氯沙坦和 PD123319 的作用。 0.5 mg/kg（静脉注射）氯沙坦消除了中枢 ANG II 诱导的升压反应。高剂量氯沙坦（5 mg/kg，静脉注射）显示出对静脉注射的升压反应增强。 ANG II，伴有心动过缓。与升压反应相关，心血管控制区域的 c-fos 表达在低剂量和高剂量氯沙坦之间存在显着差异。这些区域包括前脑的穹窿下器官、正中视前核、终板血管器和室旁核，以及后脑的孤束核、外侧臂旁核。静脉注射后，低剂量氯沙坦显着降低了这些区域的 c-fos。 ANG II，而高剂量氯沙坦与 ANG II 一起在这些区域引发了比 i.c.v. 诱导的更强的 FOS 免疫反应性。单独的ANG II。这是一个新颖的发现，即在相同条件下，大脑中的c-fos表达可以同时被激活和抑制。 PD123319 (0.8 mg/kg) 不会改变中枢 ANG II 诱导的胎儿升压反应。这些结果表明 i.c.v.高剂量和低剂量的氯沙坦对妊娠晚期胎儿中枢ANG II诱导的升压反应具有显着不同的影响，并且AT机制在胎儿心血管调节中发挥着重要作用。
The renin-angiotensin system plays an important role in cardiovascular control. Intra-cerebroventricular (i.c.v.) angiotensin (ANG) II causes a reliable pressor response in the fetus at 90% gestation. To determine the roles of brain AT(1) and AT(2) receptors in this response, the effects of the central AT(1) and AT(2) receptor antagonists losartan and PD123319 were investigated in chronically prepared near-term ovine fetuses. Losartan at 0.5 mg/kg (i.c.v.) abolished central ANG II-induced pressor responses. High-dose losartan (5 mg/kg, i.c.v.) showed a potentiation of the pressor response to i.c.v. ANG II, accompanied by bradycardia. Associated with the pressor responses, c-fos expression in the cardiovascular controlling areas was significantly different between the low and high doses of losartan. These areas included the subfornical organ, median preoptic nucleus, organum vasculosum of the lamina terminalis, and paraventricular nuclei in the forebrain, and the tractus solitarius nuclei, lateral parabrachial nuclei in the hindbrain. Low-dose losartan markedly reduced c-fos in these areas after i.c.v. ANG II, while the high-dose losartan together with ANG II elicited a much stronger FOS-immunoreactivity in these areas than that induced by i.c.v. ANG II alone. This is a novel finding, that c-fos expression in the brain can be both activated and inhibited under the same condition. Central ANG II-induced fetal pressor responses were not altered by PD123319 (0.8 mg/kg). These results indicate that i.c.v. losartan at a high and a low dose has strikingly different effects on central ANG II-induced pressor responses in fetuses at late gestation, and that the AT, mechanism plays an important role in fetal cardiovascular regulation.