Effects of peptide and non-peptide antagonists of angiotensin II receptors on drinking behavior in rats.
The effects of the non-peptide selective angiotensin II AT1 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 AT2 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 ID50 values of these drugs showed the following order of potency: EXP 3174 > saralasin > sarmesin > DuP 753 indicating their ability to block central AT1 receptors. The imidazole compound increased ANGII-induced water intake suggesting its AT1 receptor agonistic properties. PD 123319 inhibited ANGII-induced water intake at a higher dose (64 nmol), allowing to assume AT1 receptor agonistic properties.
Alova
L G
LG
Radioizotope Laboratory, Bulgarian Academy of Sciences, Sofia, Bulgaria.
Stancheva
S L
SL
Matsoukas
J
J
Georgiev
V P
VP
D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D004327:Drinking Behavior / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000502:physiology; D012504:Saralasin / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C073402:PD 123319; C040420:angiotensin II, Sar(1)-Me-Tyr(4)-; C066026:losartan carboxylic acid; D012504:Saralasin; D019808:Losartan