Toney G M, Porter J P
Department of Pharmacology, University of Texas Health Science Center, San Antonio 78282-7764.
Brain Res Dev Brain Res. 1993 Feb 19;71(2):193-9. doi: 10.1016/0165-3806(93)90171-6.
Areas of adult rat brain that mediate the cardiovascular effects of central angiotensin II (ANG II) predominantly express AT1 ANG II receptors. In contrast, AT2 receptor expression in young rats is transiently increased, reaching a maximum during the first few weeks of life. This study was designed to determine the roles of brain AT1 and AT2 receptors in mediating the central pressor effects of ANG II in young (4-week-old) conscious spontaneously hypertensive rats (SHR). Mean arterial pressure responses to intracerebroventricular (i.c.v.) ANG II (100 ng in 5 microliters) were determined 10 minutes after i.c.v. injection of either the AT1 receptor antagonist Losartan (1.0, 2.5, 5.0, and 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. Losartan prevented the pressor response to i.c.v. ANG II in a dose-dependent manner (P < 0.05), while i.c.v. PD 123319 alone was without effect. In other animals, pressor responses caused by i.c.v. ANG II-induced vasopressin secretion (VP-component) and sympathetic nervous system activation (SNS-component) were studied individually, with similar result; Losartan prevented the SNS-component, but reduced the VP-component by only 45%, indicating that both pressor components involve AT1 receptor activation. However, doses of Losartan were more effective when combined with 3.5 micrograms of PD 123319 than when given alone (P < 0.05); nearly eliminating the VP-component. These results suggest that i.c.v. ANG-II-induced pressor effects may involve activation of multiple receptor subtypes.
介导中枢血管紧张素II（ANG II）心血管效应的成年大鼠脑区主要表达AT1 ANG II受体。相比之下，幼鼠中AT2受体的表达会短暂增加，在出生后的头几周达到峰值。本研究旨在确定脑内AT1和AT2受体在介导ANG II对年轻（4周龄）清醒自发性高血压大鼠（SHR）的中枢升压作用中的作用。在脑室内（i.c.v.）注射AT1受体拮抗剂氯沙坦（1.0、2.5、5.0和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（i.c.v.）ANG II（5微升中含100纳克）的平均动脉压反应。在对照大鼠中，脑室内注射氯沙坦以剂量依赖的方式阻止了对脑室内ANG II的升压反应（P<0.05），而单独脑室内注射PD 123319则无作用。在其他动物中，分别研究了脑室内ANG II诱导的血管升压素分泌（VP成分）和交感神经系统激活（SNS成分）引起的升压反应，结果相似；氯沙坦阻止了SNS成分，但仅使VP成分降低了45%，表明两种升压成分均涉及AT1受体激活。然而，氯沙坦与3.5微克PD 123319联合使用时比单独使用更有效（P<0.05）；几乎消除了VP成分。这些结果表明，脑室内ANG-II诱导的升压作用可能涉及多种受体亚型的激活。
