Toney G M, Porter J P
Department of Pharmacology, University of Texas Health Science Center, San Antonio 78282-7764.
Brain Res. 1993 Feb 12;603(1):57-63. doi: 10.1016/0006-8993(93)91299-8.
Intracerebroventricular (i.c.v.) angiotensin II (ANG II) increases vascular resistance and elicits a pressor response characterized by sympathetic nervous system activation (SNS component) and increased vasopressin (VP) secretion (VP component). This study examines the role of brain AT1 and AT2 ANG II receptors in mediating the pressor and renal hemodynamic effects of i.c.v. ANG II in conscious Sprague-Dawley rats. Mean arterial pressure, heart rate and renal vascular resistance responses to i.c.v. ANG II (100 ng in 5 microliters) were determined 10 min after i.c.v. injection of either the AT1 receptor antagonist, DuP 753 (1.0, 2.5, 5.0, 10.0 micrograms), the AT2 receptor ligand, PD 123319 (3.5 x [10(-6), 10(-4), 10(-2), 10(0)] micrograms), or both. In control rats, i.c.v. DuP 753 prevented the pressor response and the increase in renal vascular resistance that occurred following i.c.v. ANG II in a dose-dependent manner (P < 0.05), while i.c.v. PD 123319 was without affect. When the VP- and SNS components were studied individually, by preventing the SNS component with intravenous (i.v.) chlorisondamine or the VP component with a V1 receptor antagonist (i.v.) similar results were obtained; DuP 753 prevented the SNS component and significantly reduced the VP component. These results indicate that both central ANG II pressor components are mediated primarily by brain AT1 receptors. However, doses of DuP 753 were more effective when combined with 3.5 micrograms of PD 123319 than when given alone (P < 0.05), suggesting that the pressor effects of i.c.v. ANG II may involve activation of multiple ANG II receptor subtypes.
脑室内注射血管紧张素II（ANG II）可增加血管阻力，并引发以交感神经系统激活（交感神经成分）和血管加压素（VP）分泌增加（VP成分）为特征的升压反应。本研究探讨了脑内AT1和AT2血管紧张素II受体在介导清醒Sprague-Dawley大鼠脑室内注射ANG II的升压和肾血流动力学效应中的作用。在脑室内注射AT1受体拮抗剂DuP 753（1.0、2.5、5.0、10.0微克）、AT2受体配体PD 123319（3.5×[10(-6)、10(-4)、10(-2)、10(0)]微克）或两者后10分钟，测定对脑室内注射ANG II（5微升中含100纳克）的平均动脉压、心率和肾血管阻力反应。在对照大鼠中，脑室内注射DuP 753以剂量依赖性方式（P<0.05）阻止了脑室内注射ANG II后出现的升压反应和肾血管阻力增加，而脑室内注射PD 123319则无影响。当分别研究VP和交感神经成分时，通过静脉注射氯异吲哚胺阻止交感神经成分或通过V1受体拮抗剂静脉注射阻止VP成分，得到了类似的结果；DuP 753阻止了交感神经成分并显著降低了VP成分。这些结果表明，两种中枢ANG II升压成分主要由脑内AT1受体介导。然而，DuP 753与3.5微克PD 123319联合使用时比单独使用更有效（P<0.05），这表明脑室内注射ANG II的升压作用可能涉及多种ANG II受体亚型的激活。
