Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata City, Niigata 951-8510, Japan.
Endocr J. 2011;58(7):559-73. doi: 10.1507/endocrj.k11e-002. Epub 2011 Apr 29.
The anteroventral third ventricular region (AV3V) is a pivotal area for osmotic responses and integration of autonomic functions. The purpose of this study was to investigate whether the gamma-aminobutyric acid (GABA)-ergic activity in the AV3V may be involved in the regulation of arginine vasopressin (AVP) secretion and related phenomena under the conditions with or without hypovolemia. Experiments were performed in conscious rats. We found that AV3V infusion with the GABA(A) receptor antagonist bicuculline in euvolemic rats caused prompt increases in plasma AVP, osmolality, glucose, arterial pressure and heart rate. The effects of the bicuculline infusion were abolished by prior infusion of a GABA(A) receptor agonist, muscimol. When repeated twice with a 10-min interval, removal of systemic blood (10 mL/kg body weight) lowered arterial pressure and enhanced plasma AVP, osmolality, glucose and angiotensin II. Muscimol infusion in the AV3V, but not in the cerebral ventricle, inhibited the responses of plasma AVP and glucose, despite having no effect in a sham hemorrhagic state. The inhibition of the AVP response by the muscimol infusion was also verified in rats given a combined stimulus of bleeding plus an osmotic load. In contrast, AV3V infusion with the GABA(B) receptor agonist baclofen tended to intensify the hemorrhagic responses of plasma AVP and glucose, despite its potency to prevent the hemorrhagic fall in arterial pressure. These results, taken together with our previous data, suggest that hypovolemic stimuli, like hyperosmotic stimuli, may promote AVP secretion by causing the inhibition of AV3V GABA(A)-ergic activity responsible for potentiation of glutamatergic activity.
第三脑室前腹侧区（AV3V）是渗透反应和自主功能整合的关键区域。本研究旨在探讨 AV3V 中的γ-氨基丁酸（GABA）能活性是否参与调节低血容量或不伴低血容量条件下的血管加压素（AVP）分泌和相关现象。实验在清醒大鼠中进行。我们发现，在等容大鼠中 AV3V 内输注 GABA A 受体拮抗剂荷包牡丹碱会立即引起血浆 AVP、渗透压、葡萄糖、动脉压和心率升高。荷包牡丹碱输注的作用被 GABA A 受体激动剂 muscimol 预先输注所消除。当两次重复间隔 10 分钟时，去除全身血液（10 mL/kg 体重）会降低动脉压并增强血浆 AVP、渗透压、葡萄糖和血管紧张素 II。Muscimol 在 AV3V 内输注，但不在脑室内输注，尽管在假性出血状态下没有作用，但抑制了血浆 AVP 和葡萄糖的反应。在给予出血加渗透负荷联合刺激的大鼠中，也验证了 muscimol 输注对 AVP 反应的抑制作用。相比之下，AV3V 内输注 GABA B 受体激动剂 baclofen 倾向于增强出血引起的血浆 AVP 和葡萄糖反应，尽管其有预防动脉压低的作用。这些结果与我们之前的数据一起表明，低血容量刺激，如高渗刺激，可能通过引起负责增强谷氨酸能活性的 AV3V GABA A 能活性的抑制来促进 AVP 分泌。
