Morita O, Kushida H, Kunihara M
Tsukuba Research Laboratory, Upjohn Pharmaceuticals, Japan.
J Cardiovasc Pharmacol. 1995 Jun;25(6):880-7. doi: 10.1097/00005344-199506000-00005.
We examined the effects of U-97018, an AT1 receptor antagonist, on the pressor response to intracerebroventricularly (i.c.v.) administered angiotensin II (AII) in conscious normotensive rats in comparison to losartan, EXP 3174, EXP 655, and saralasin. In an i.c.v. study, U-97018, losartan, and EXP 3174 reduced the pressor response. EXP 655, an AT2 selective antagonist, also inhibited the pressor response to i.c.v. AII. U-97018 combined with EXP 655 did not fully eliminate the pressor response to i.c.v. AII. Moreover, saralasin, a nonselective peptide AII antagonist, also failed to abolish the pressor response to i.c.v. AII. Therefore, both AT1- and AT2-receptors probably are functional in inhibiting the pressor response to i.c.v. AII and that a part of the i.c.v. AII-induced pressor response occurs through non-AT1- and non-AT2-receptors. In an intravenous (i.v.) study, U-97018, losartan, and EXP 3174 reduced the pressor response to i.c.v. AII. At 10 mg/kg orally (p.o.), which is an antihypertensive dose in spontaneously hypertensive rats (SHR), neither U-97018 nor losartan reduced the pressor response to i.c.v. AII even at 180 min after administration. This result indicates that neither U-97018 nor losartan, at the oral antihypertensive dose, reaches the brain in sufficient amount to affect the pressor response to i.c.v. AII.
我们研究了AT1受体拮抗剂U-97018对清醒正常血压大鼠脑室内（i.c.v.）注射血管紧张素II（AII）所致升压反应的影响，并与氯沙坦、EXP 3174、EXP 655和沙拉新进行了比较。在一项i.c.v.研究中，U-97018、氯沙坦和EXP 3174降低了升压反应。AT2选择性拮抗剂EXP 655也抑制了对i.c.v. AII的升压反应。U-97018与EXP 655联合使用并未完全消除对i.c.v. AII的升压反应。此外，非选择性肽类AII拮抗剂沙拉新也未能消除对i.c.v. AII的升压反应。因此，AT1和AT2受体可能都在抑制对i.c.v. AII的升压反应中发挥作用，且部分i.c.v. AII诱导的升压反应是通过非AT1和非AT2受体发生的。在一项静脉内（i.v.）研究中，U-97018、氯沙坦和EXP 3174降低了对i.c.v. AII的升压反应。在10mg/kg口服（p.o.）剂量下，这是自发性高血压大鼠（SHR）的抗高血压剂量，即使在给药后180分钟，U-97018和氯沙坦也未降低对i.c.v. AII的升压反应。该结果表明，在口服抗高血压剂量下，U-97018和氯沙坦均未足量到达脑内以影响对i.c.v. AII的升压反应。
