Unger T, Bles F, Ganten D, Lang R E, Rettig R, Schwab N A
Eur J Pharmacol. 1983 May 20;90(1):1-9. doi: 10.1016/0014-2999(83)90207-8.
In conscious rats, intracerebroventricular (i.c.v.) treatment with the GABA agonist muscimol (1-100 ng) suppressed the pressor responses to ANG II (100 ng i.c.v.) in a dose-dependent and reversible fashion. Treatment i.c.v. with GABA (1-500 micrograms) produced a similar but shorter inhibition. Inhibition of endogenous GABA degradation with amino-oxyacetic acid (AOAA, 30 mg/kg i.p.) markedly reduced the pressor responses to ANG II (10-1000 ng i.c.v.) with a recovery period of 24 h. This inhibition was reversed by the GABA antagonist bicuculline (1 microgram i.c.v.). Muscimol (100 ng i.c.v.) did not significantly attenuate the pressor responses to i.c.v. histamine (10 micrograms). Pretreatment with muscimol (100 ng i.c.v.) drastically reduced the drinking responses to i.c.v. ANG II (500 ng) and increased the latency to drink. Muscimol also suppressed drinking induced by carbachol (50 ng i.c.v.). Muscimol (10-1000 ng i.c.v.) inhibited the ANG II (100 ng i.c.v.)-induced release of AVP from the pituitary gland with complete suppression of the response at the highest dose. Our results demonstrate that the GABAergic system exerts an inhibitory control on pathways mediating the various central actions of ANG II, which appears to be most specific for the ANG II-induced pressor responses.
在清醒大鼠中，脑室内（i.c.v.）给予GABA激动剂蝇蕈醇（1 - 100 ng）以剂量依赖性和可逆方式抑制了对血管紧张素II（i.c.v.给予100 ng）的升压反应。脑室内给予GABA（1 - 500微克）产生了类似但持续时间较短的抑制作用。用氨氧乙酸（AOAA，腹腔注射30 mg/kg）抑制内源性GABA降解，显著降低了对血管紧张素II（i.c.v.给予10 - 1000 ng）的升压反应，恢复期为24小时。这种抑制作用可被GABA拮抗剂荷包牡丹碱（i.c.v.给予1微克）逆转。蝇蕈醇（i.c.v.给予100 ng）并未显著减弱对i.c.v.组胺（10微克）的升压反应。用蝇蕈醇（i.c.v.给予100 ng）预处理可显著降低对i.c.v.血管紧张素II（500 ng）的饮水反应，并延长饮水潜伏期。蝇蕈醇还抑制了卡巴胆碱（i.c.v.给予50 ng）诱导的饮水。蝇蕈醇（i.c.v.给予10 - 1000 ng）抑制血管紧张素II（i.c.v.给予100 ng）诱导的垂体后叶素释放，在最高剂量时完全抑制反应。我们的结果表明，GABA能系统对介导血管紧张素II各种中枢作用的途径发挥抑制性控制，这似乎对血管紧张素II诱导的升压反应最为特异。
