血管紧张素II受体的肽类和非肽类拮抗剂对大鼠饮水行为的影响。

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

作者信息

Alova L G, Stancheva S L, Matsoukas J, Georgiev V P

机构信息

Radioizotope Laboratory, Bulgarian Academy of Sciences, Sofia, Bulgaria.

出版信息

J Physiol Paris. 1999 May-Jun;93(3):219-24. doi: 10.1016/s0928-4257(99)80154-5.

DOI:10.1016/s0928-4257(99)80154-5

PMID:10399677

Abstract

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.

摘要

研究了非肽类选择性血管紧张素II AT1受体拮抗剂DuP 753及其代谢产物EXP 3174、肽类血管紧张素II类似物沙拉新和萨米辛以及新合成的咪唑化合物（1-甲基-4,5-二苯基咪唑）对大鼠血管紧张素II诱导饮水的影响。还研究了AT2选择性拮抗剂PD 123319对大鼠血管紧张素II诱导饮水的影响。DuP 753、EXP 3174、沙拉新和萨米辛（肽类和非肽类）均剂量依赖性地抑制血管紧张素II诱导的水摄入量。这些药物的半数抑制剂量（ID50）值显示出以下效价顺序：EXP 3174 > 沙拉新 > 萨米辛 > DuP 753，表明它们阻断中枢AT1受体的能力。咪唑化合物增加了血管紧张素II诱导的水摄入量，表明其具有AT1受体激动特性。PD 123319在较高剂量（64 nmol）时抑制血管紧张素II诱导的水摄入量，提示其具有AT1受体激动特性。