Baltatu O, Fontes M A, Campagnole-Santos M J, Caligiorni S, Ganten D, Santos R A, Bader M
Max Delbrück Center for Molecular Medicine, D-13092 Berlin-Buch, Germany.
Am J Physiol Regul Integr Comp Physiol. 2001 Feb;280(2):R428-33. doi: 10.1152/ajpregu.2001.280.2.R428.
The transgenic rats TGR(ASrAOGEN) (TGR) with low levels of brain angiotensinogen were analyzed for cardiovascular reactivity to microinjections of ANG II and angiotensin receptor (AT(1)) antagonists [CV-11974, AT(1) specific; A-779, ANG-(1--7) selective; sarthran, nonspecific] into the rostral ventrolateral medulla (RVLM) of conscious rats. Microinjection of ANG II resulted in a significantly higher increase in the mean arterial pressure (MAP) of TGR than control [Sprague-Dawley (SD)] rats, suggesting an upregulation of ANG II receptors in TGR. CV-11974 produced an increase in MAP of SD but not in TGR rats. A-779 produced a depressor response in SD but not in TGR rats. Conversely, sarthran produced a similar decrease of MAP in both rat groups. The pressor effect of the AT(1) antagonist may indicate an inhibitory role of AT(1) receptors in the RVLM. On the other hand, ANG-(1--7) appears to have a tonic excitatory role in this region. The altered response to specific angiotensin antagonists in TGR further supports the functionally relevant decrease in angiotensins in the brains of TGR and corroborates the importance of the central renin-angiotensin system in cardiovascular homeostasis.
对脑内血管紧张素原水平较低的转基因大鼠TGR(ASrAOGEN)(TGR)进行分析，观察其对向清醒大鼠延髓头端腹外侧区(RVLM)微量注射血管紧张素II(ANG II)和血管紧张素受体(AT(1))拮抗剂[CV - 11974，AT(1)特异性；A - 779，ANG-(1 - 7)选择性；sarthran，非特异性]时的心血管反应。微量注射ANG II后，TGR大鼠的平均动脉压(MAP)升高幅度显著高于对照[斯普拉格-道利(SD)]大鼠，提示TGR中ANG II受体上调。CV - 11974使SD大鼠的MAP升高，但对TGR大鼠无此作用。A - 779使SD大鼠出现降压反应，但对TGR大鼠无此作用。相反，sarthran使两组大鼠的MAP出现相似程度的降低。AT(1)拮抗剂的升压作用可能表明AT(1)受体在RVLM中具有抑制作用。另一方面，ANG-(1 - 7)在该区域似乎具有紧张性兴奋作用。TGR对特异性血管紧张素拮抗剂反应的改变进一步支持了TGR脑内血管紧张素功能相关的减少，并证实了中枢肾素-血管紧张素系统在心血管稳态中的重要性。
