Sessler F M, Mah E J, Grady S M
Department of Physiology & Biophysics, Hahnemann University, Philadelphia, PA 19102-1192.
Brain Res. 1993 Jun 11;613(2):259-68. doi: 10.1016/0006-8993(93)90907-5.
The lateral hypothalamus (LH) is involved in the central integration of fluid and electrolyte balance. Several studies have suggested a role for norepinephrine (NE) in these functions. In previous studies we presented evidence in support of a modulatory role for NE within the LH circuitry. Specifically, NE facilitated responses of LH cells to synaptic inputs and putative transmitters. In the present studies, we examined the influence of NE on the response of LH neurons to the inhibitory amino acid transmitter GABA. Neuronal responses were studied in normal, DOCA hypertensive, and 1% NaCl diet (HSD)-treated rats. Male rats were uninephrectomized and received a DOCA implant (200 mg/kg). They were given 1% NaCl and 0.1% KCl in their drinking water (4-6 weeks). HSD rats received the same treatment, except that no DOCA was given. Extracellularly recorded responses from single LH neurons to iontophoretic pulses (5-50 nA; 10 s duration) of GABA were examined before, during and after NE microiontophoresis (5-50 nA) in anesthetized rats. The results indicated a shift of NE modulatory action from potentiating to antagonizing GABA-induced inhibition. In control rats, NE routinely potentiated GABA depressant responses (19 of 26, 73%), whereas in HSD rats the ability of NE to enhance GABA responses was reduced to 33% of the cases tested (10 of 30). Likewise, NE did not augment, but rather antagonized GABA inhibition in the majority of cells recorded (21 of 35, 60%) from DOCA hypertensive rats. The beta agonist isoproterenol was still capable of potentiating GABA inhibition of LH cells in HSD and DOCA treated animals, suggesting that the change in the capacity of NE to enhance GABA action is not a result of alterations in beta receptor function, but could arise from a modification of the ratio between alpha- and beta-adrenoceptors. NE modulating capability was also altered-in LH neurons responsive to experimentally induced changes in blood pressure. In summary, these findings suggest that chronic HSD and DOCA treatments can alter the modulatory capacities of NE within the LH. These alterations in noradrenergic action within hypothalamic cardiovascular centers might affect the way neurons respond to afferent baroreceptor information, as well as the way they control sympathetic and parasympathetic effector mechanisms. A decrease in the inhibitory capacities of GABA transmission in these areas, due to alterations of NE, may play a role in the genesis of hypertension.
外侧下丘脑（LH）参与体液和电解质平衡的中枢整合。多项研究表明去甲肾上腺素（NE）在这些功能中发挥作用。在先前的研究中，我们提供了证据支持NE在LH神经回路中的调节作用。具体而言，NE促进了LH细胞对突触输入和假定递质的反应。在本研究中，我们研究了NE对LH神经元对抑制性氨基酸递质γ-氨基丁酸（GABA）反应的影响。在正常大鼠、去氧皮质酮（DOCA）高血压大鼠和1%氯化钠饮食（HSD）处理的大鼠中研究了神经元反应。雄性大鼠进行单侧肾切除并植入DOCA（200mg/kg）。它们的饮用水中含有1%氯化钠和0.1%氯化钾（4-6周）。HSD大鼠接受相同的处理，但未给予DOCA。在麻醉大鼠中，在NE微量离子导入（5-50nA）之前、期间和之后，检查单个LH神经元对GABA离子导入脉冲（5-50nA；持续10秒）的细胞外记录反应。结果表明NE的调节作用从增强GABA诱导的抑制转变为拮抗作用。在对照大鼠中，NE通常增强GABA的抑制反应（26例中的19例，73%），而在HSD大鼠中，NE增强GABA反应的能力降至测试病例的33%（30例中的10例）。同样，在DOCA高血压大鼠记录的大多数细胞（35例中的21例，60%）中，NE不是增强而是拮抗GABA的抑制作用。β激动剂异丙肾上腺素在HSD和DOCA处理的动物中仍能够增强GABA对LH细胞的抑制作用，这表明NE增强GABA作用能力的变化不是β受体功能改变的结果，而是可能源于α-和β-肾上腺素能受体之间比例的改变。在对实验诱导的血压变化有反应的LH神经元中，NE的调节能力也发生了改变。总之，这些发现表明慢性HSD和DOCA处理可以改变LH内NE的调节能力。下丘脑心血管中枢去甲肾上腺素能作用的这些改变可能会影响神经元对传入压力感受器信息的反应方式，以及它们控制交感和副交感效应机制的方式。由于NE的改变，这些区域GABA传递抑制能力的降低可能在高血压的发生中起作用。
