Magrì V, Trimarchi G R, Quattrone G, Squadrito F, Di Giorgio R M, Costa G, Caputi A P
Res Commun Chem Pathol Pharmacol. 1984 Jul;45(1):107-18.
Cerebral glutamate decarboxylase (GAD) activity in DOCA-salt hypertensive rats showed a significant increase in the mesencephalon and a significant decrease in the cerebral cortex and in the cerebellum, compared to that observed in mononephrectomized normotensive animals. Intracerebroventricular (icv) injection of muscimol (0.5, 1 and 2 micrograms), a GABA receptor agonist, produced a dose-dependent decrease in heart rate (HR), significantly greater in freely moving hypertensive animals than in normotensive controls. Muscimol also reduced mean arterial pressure (MAP). The hypotensive effect induced by muscimol (2 micrograms) was significantly higher in hypertensive animals. Ethanolamine-O-sulphate (5, 10, 20 and 40 microM), an inhibitor of GABA breakdown, determined a decrease in MAP and in HR greater in hypertensive than in normotensive rats. Intraperitoneal injection of valproic acid (50-100 mg/Kg/die) for 6 weeks significantly reduced the development of DOCA-salt hypertension in rats. The anti-hypertensive effect became significant during the 4th week and was dose-dependent. DOCA-salt animals, daily treated with 50 mg/Kg of valproic acid, showed an increased pressor response to intravenous injection of phenylephrine (0.1, 0.5 and 1 microgram/Kg). Data strongly support an impairment of cerebral GABA control of blood pressure and heart rate in DOCA-salt hypertensive rats.
与单肾切除的正常血压动物相比，去氧皮质酮-盐高血压大鼠的脑谷氨酸脱羧酶（GAD）活性在中脑显著增加，而在大脑皮层和小脑中显著降低。脑室注射（icv）GABA受体激动剂蝇蕈醇（0.5、1和2微克）可使心率（HR）呈剂量依赖性降低，在自由活动的高血压动物中比正常血压对照组更显著。蝇蕈醇还可降低平均动脉压（MAP）。蝇蕈醇（2微克）诱导的降压作用在高血压动物中显著更高。乙醇胺-O-硫酸盐（5、10、20和40微摩尔）是一种GABA分解抑制剂，可使高血压大鼠的MAP和HR降低幅度大于正常血压大鼠。腹腔注射丙戊酸（50 - 100毫克/千克/天）持续6周可显著降低大鼠去氧皮质酮-盐高血压的发展。抗高血压作用在第4周开始显著且呈剂量依赖性。每天用50毫克/千克丙戊酸治疗的去氧皮质酮-盐动物对静脉注射去氧肾上腺素（0.1、0.5和1微克/千克）的升压反应增强。数据有力地支持了去氧皮质酮-盐高血压大鼠脑内GABA对血压和心率的控制受损。
