Georgiev V P, Klusha V E, Getova D P, Petkov V D, Svirskis S V, Mutsenietse R K, Kambourova T S, Oppitz M Zh, Ancans J E
Institute of Physiology, Bulgarian Academy of Sciences, Sofia.
Acta Physiol Pharmacol Bulg. 1988;14(1):22-9.
The effects of the newly-synthesized AT II analogue (Sar1 azaVal3 Ile8) AT II were investigated in comparison with the octapeptide AT II and the analogue saralazin (Sar1 Ala8) AT II, using intracerebroventricular administration, with respect to the following parameters: the level of biogenic monoamines (DA, NA and 5-HT) and the metabolites HVA and 5-HIAA in mouse forebrain; the behaviour of the animals--cataleptogenic actions of mice, PTZ convulsive--seizure threshold in mice, apomorphine stereotypy in rats and behaviour of rats in a conflict situation. The analogue (Sar1 azaVal3 Ile8) AT II, unlike saralazin and AT II, was found to induce a rise in the NA and 5-HT levels, causing also catalepsy that is different from the catalepsy induced by saralazine, AT II and haloperidol, because of its rapid onset and decline; it increases the PTZ convulsive--seizure threshold and reduces the number of punished responses to the conflict drinking test (anxiomimetic effect) in a dose 20 times lower than the dose inducing the remaining effects. This effect was antagonized by saralazine. It is concluded that the newly-synthesized analogue (Sar1 azaVal3 Ile8) AT II induces effects similar to those caused by AT II, being at the same time different to a certain extent from the effects (quantitative and qualitative) of octapeptide AT II.
通过脑室内给药,比较了新合成的血管紧张素II类似物(Sar1 azaVal3 Ile8)血管紧张素II与八肽血管紧张素II及类似物沙拉新(Sar1 Ala8)血管紧张素II在以下参数方面的作用:小鼠前脑生物源性单胺(多巴胺、去甲肾上腺素和5-羟色胺)及其代谢产物高香草酸和5-羟吲哚乙酸的水平;动物行为——小鼠的僵住症诱发作用、戊四氮惊厥——小鼠的惊厥阈值、大鼠的阿扑吗啡刻板行为以及大鼠在冲突情境中的行为。结果发现,与沙拉新和血管紧张素II不同,类似物(Sar1 azaVal3 Ile8)血管紧张素II可使去甲肾上腺素和5-羟色胺水平升高,还会引发僵住症,该僵住症与沙拉新、血管紧张素II及氟哌啶醇诱发的僵住症不同,因其起效快且消退快;它能提高戊四氮惊厥——惊厥阈值,并在比诱发其他效应剂量低20倍的剂量下,减少冲突饮水试验中受惩罚反应的次数(拟焦虑效应)。这种效应被沙拉新拮抗。结论是,新合成的类似物(Sar1 azaVal3 Ile8)血管紧张素II诱发的效应与血管紧张素II所致效应相似,同时在一定程度上与八肽血管紧张素II的效应(数量和质量方面)有所不同。