Effects of peptide and non-peptide antagonists of angiotensin II receptors on drinking behavior in rats.

Abstract The effects of the non-peptide selective angiotensin II AT 1 receptor antagonist DuP 753 and its metabolite EXP 3174, of the peptide ANGII analogues saralasin and sarmesin and of the newly synthesized imidazole compound (1-methyl-4,5-diphenylimidazole) on ANGII-induced drinking in rats were investigated. The effect of the AT 2 selective antagonist PD 123319 on ANGII-induced drinking in rats was also studied. DuP 753, EXP 3174, saralasin and sarmesin (peptides and non-peptides) dose-dependently inhibited ANGII-induced water intake. The ID 50 values of these drugs showed the following order of potency: EXP 3174 > saralasin > sarmesin > DuP 753 indicating their ability to block central AT 1 receptors. The imidazole compound increased ANGII-induced water intake suggesting its AT 1 receptor agonistic properties. PD 123319 inhibited ANGII-induced water intake at a higher dose (64 nmol), allowing to assume AT 1 receptor agonistic properties.