O. Morita et al., EFFECTS OF U-9701X ON PRESSOR-RESPONSES TO INTRACEREBROVENTRICULARLY ADMINISTERED ANGIOTENSIN-II IN CONSCIOUS NORMOTENSIVE RATS, Journal of cardiovascular pharmacology, 25(6), 1995, pp. 880-887
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.