EFFECTS OF U-9701X ON PRESSOR-RESPONSES TO INTRACEREBROVENTRICULARLY ADMINISTERED ANGIOTENSIN-II IN CONSCIOUS NORMOTENSIVE RATS

We examined the effects of U-97018, an AT(1) receptor antagonist, on t he presser 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-9701 8, losartan, and EXP 3174 reduced the presser response. EXP 655, an AT (2) selective antagonist, also inhibited the presser response to i.c.v . AII. U-97018 combined with EXP 655 did not fully eliminate the press er response to i.c.v. AII. Moreover, saralasin, a nonselective peptide AII antagonist, also failed to abolish the presser response to i.c.v. AII. Therefore, both AT(1)- and AT(2)-receptors probably are function al in inhibiting the presser response to i.c.v. AII and that a part of the i.c.v. AII-induced presser response occurs through non-AT(1)- and non-AT(2)-receptors. In an intravenous (i.v.) study, U-97018, losarta n, and EXP 3174 reduced the presser response to i.c.v. AII. At 10 mg/k g orally (p.o.), which is an antihypertensive dose in spontaneously hy pertensive rats (SHR), neither U-97018 nor losartan reduced the presse r response to i.c.v. AII even at 180 min after administration. This re sult indicates that neither U-97018 nor losartan, at the oral antihype rtensive dose, reaches the brain in sufficient amount to affect the pr esser response to i.c.v. AII.