Wible J H, DiMicco J A, Luft F C
Department of Pharmacology, Indiana University School of Medicine, Indianapolis 46202-5120.
Hypertension. 1989 Dec;14(6):623-8. doi: 10.1161/01.hyp.14.6.623.
The posterior hypothalamus contains a sympathoexcitatory system that can be modulated by changes in GABAergic tone. We tested the hypothesis that the GABAergic mechanism in the posterior hypothalamus is altered in spontaneously hypertensive rats (SHR) compared with the Wistar-Kyoto (WKY) control rats. Blood pressure and heart rate were continuously measured in the conscious state; blood samples were obtained for determination of plasma catecholamine concentrations. Bilateral microinjections of the GABAA receptor antagonist bicuculline methiodide into the posterior hypothalamus increased heart rate and blood pressure in a dose-related fashion and increased plasma catecholamine concentrations in both SHR and WKY rats. The responses were not significantly different between the two strains of rats. Microinjections of the GABAA receptor agonist muscimol in this same region caused dose-related decreases in both heart rate and blood pressure in SHR and WKY rats. Although the decreases in heart rate caused by muscimol were not significantly different between the SHR and WKY rats, the decreases in blood pressure were significantly greater in SHR compared with WKY rats. Further, microinjection of muscimol caused a significant decrease in plasma catecholamines in SHR but not in WKY rats. These data indicate that in SHR and WKY rats the posterior hypothalamus contains a sympathoexcitatory mechanism that is tonically inhibited by GABA. The ability of muscimol to decrease plasma catecholamines selectively in SHR and to cause greater decreases in blood pressure, suggests that the GABAergic mechanisms in the posterior hypothalamus of the SHR and WKY rats may differ.
下丘脑后部包含一个交感兴奋系统，该系统可受γ-氨基丁酸（GABA）能张力变化的调节。我们检验了这样一个假设：与Wistar-Kyoto（WKY）对照大鼠相比，自发性高血压大鼠（SHR）下丘脑后部的GABA能机制发生了改变。在清醒状态下连续测量血压和心率；采集血样以测定血浆儿茶酚胺浓度。向SHR和WKY大鼠的下丘脑后部双侧微量注射GABAA受体拮抗剂甲基荷包牡丹碱，可使心率和血压呈剂量相关增加，并使血浆儿茶酚胺浓度升高。两种品系大鼠的反应无显著差异。在同一区域微量注射GABAA受体激动剂蝇蕈醇，可使SHR和WKY大鼠的心率和血压呈剂量相关下降。虽然蝇蕈醇引起的SHR和WKY大鼠心率下降无显著差异，但与WKY大鼠相比，SHR大鼠的血压下降幅度显著更大。此外，微量注射蝇蕈醇可使SHR大鼠的血浆儿茶酚胺显著降低，但对WKY大鼠则无此作用。这些数据表明，在SHR和WKY大鼠中，下丘脑后部含有一种交感兴奋机制，该机制受到GABA的紧张性抑制。蝇蕈醇能够选择性降低SHR大鼠的血浆儿茶酚胺，并导致更大幅度的血压下降，这表明SHR和WKY大鼠下丘脑后部的GABA能机制可能存在差异。
