Department of Physiological Sciences, Center of Biological Sciences, State University of Londrina Londrina, Brazil.
Front Physiol. 2013 Jan 9;3:490. doi: 10.3389/fphys.2012.00490. eCollection 2012.
The paraventricular nucleus (PVN) of the hypothalamus is an important site for autonomic and neuroendocrine regulation. Experiments in anesthetized animals and in vitro indicate an interaction among gamma-aminobutyric acid (GABA), nitric oxide (NO), and glutamate in the PVN. The cardiovascular role of the PVN and interactions of these neurotransmitters in conscious animals have not been evaluated fully. In chronically instrumented conscious rats, mean arterial pressure (MAP) and heart rate (HR) responses to microinjections (100 nl) in the region of the PVN were tested. Bilateral blockade of ionotropic excitatory amino acid (EAA) receptors (kynurenic acid, Kyn) in the PVN produced small but significant decreases in MAP and HR. GABA(A) receptor blockade (bicuculline, Bic), and inhibition of NO synthase [(NOS), N-(G)-monomethyl-L-arginine, L-NMMA] each increased MAP and HR. The NO donor sodium nitroprusside (SNP) produced depressor responses that were attenuated by Bic. NOS inhibition potentiated both pressor responses to the selective EAA agonist, N-methyl-D-aspartic acid (NMDA), and depressor responses to Kyn. Increases in MAP and HR due to Bic were blunted by prior blockade of EAA receptors. Thus, pressor responses to GABA blockade require EAA receptors and GABA neurotransmission contributes to NO inhibition. Tonic excitatory effects of glutamate in the PVN are tonically attenuated by NO. These data demonstrate that, in the PVN of conscious rats, GABA, glutamate, and NO interact in a complex fashion to regulate arterial pressure and HR under normal conditions.
下丘脑室旁核（PVN）是自主神经和神经内分泌调节的重要部位。麻醉动物和体外实验表明，PVN 中的γ-氨基丁酸（GABA）、一氧化氮（NO）和谷氨酸之间存在相互作用。PVN 中的心血管作用以及这些神经递质在清醒动物中的相互作用尚未得到充分评估。在慢性仪器化清醒大鼠中，测试了在 PVN 区域进行微注射（100nl）时的平均动脉压（MAP）和心率（HR）反应。PVN 中的离子型兴奋性氨基酸（EAA）受体（犬尿氨酸，Kyn）的双侧阻断产生了 MAP 和 HR 的微小但显著降低。GABA(A)受体阻断（印防己毒素，Bic）和一氧化氮合酶抑制[（NOS），N-（G）-单甲基-L-精氨酸，L-NMMA]均增加了 MAP 和 HR。NO 供体硝普钠（SNP）产生降压反应，Bic 可减弱该反应。NOS 抑制增强了选择性 EAA 激动剂 N-甲基-D-天冬氨酸（NMDA）的升压反应和 Kyn 的降压反应。Bic 引起的 MAP 和 HR 增加被 EAA 受体阻断所削弱。因此，GABA 阻断的升压反应需要 EAA 受体，而 GABA 神经传递有助于抑制 NO。谷氨酸在 PVN 中的紧张性兴奋作用被 NO 紧张性抑制。这些数据表明，在清醒大鼠的 PVN 中，GABA、谷氨酸和 NO 以复杂的方式相互作用，在正常情况下调节动脉血压和 HR。
