Effects of peptide and non-peptide antagonists of angiotensin II receptorson drinking behavior in rats

The effects of the non-peptide selective angiotensin II AT, receptor antago nist DuP 753 and its metabolite EXP 3174, of the peptide ANGII analogues sa ralasin and sarmesin and of the newly synthesized imidazole compound (1-met hyl-4,5-diphenylimidazole) on ANGII-induced drinking in rats were investiga ted. The effect of the AT, selective antagonist PD 123319 on ANGII-induced drinking in rats was also studied. DuP 753, EXP 3174, saralasin and sarmesi n (peptides and non-peptides) dose-dependently inhibited ANGII-induced wate r intake. The ID50 values of these drugs showed the following order of pote ncy: EXP 3174 > saralasin > sarmesin > DuP 753 indicating their ability to block central AT(1) receptors. The imidazole compound increased ANGII-induc ed water intake suggesting its AT(1) receptor agonistic properties. PD 1233 19 inhibited ANGII-induced water intake at a higher dose (64 nmol), allowin g to assume AT(1) receptor agonistic properties. (C) Elsevier, Paris.