Stimulation of cardiac sympathetic afferents activates glutamatergic neurons in the parabrachial nucleus: Relation to neurons containing nNOS
Stimulation of cardiac sympathetic afferents activates glutamatergic neurons in the parabrachial nucleus: Relation to neurons containing nNOS
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DOI：
10.1016/j.brainres.2005.06.051
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发表时间：
2005-08-16
期刊：
影响因子：
2.9
通讯作者：
Longhurst, JC
中科院分区：
文献类型：
--
作者：
Guo, ZL;Moazzami, AR;Longhurst, JC
我们之前的研究表明，刺激心脏交感传入神经会激活臂旁核（PBN）中的神经元，该区域已知在心血管自主反射的中枢整合中发挥作用。然而，这些激活神经元的表型尚未得到很好的鉴定。谷氨酸是大脑中重要的兴奋性神经递质，参与PBN介导的心血管反应。最近对囊泡谷氨酸转运蛋白 3 (VGLUT3) 的鉴定为定位使用谷氨酸作为神经递质的神经元的独特核周提供了一种新颖且独特的标记。谷氨酸在大脑中的作用受到一氧化氮的影响。因此，本研究使用三重免疫荧光标记，检测了心脏交感神经传入刺激后，PBN 中含有 VGLUT3 和神经元一氧化氮合酶 (nNOS) 的神经元中 c-Fos（一种即早期基因）的表达。在双侧压力神经支配和颈部迷走神经切断术的麻醉猫中，在左心室局部施用缓激肽（BK，1-10μg/ml，50μl，n = 6），每20分钟一次，六次。重复施用 BK 会在 100 分钟内引起血压持续升高，而用 BK 载体治疗的动物（0.9% 盐水，n = 5）则没有发现任何变化。与对照猫相比，BK 处理的动物含有 VGLUT3 的细胞体以及外侧 PBN (elPBN) 中的 VGLUT3 和 nNOS 表达显着增加（均 P < 0.01）。此外，使用类似的三重染色方法，我们注意到在 BK 刺激后，elPBN 中含有 nNOS 的激活神经元纤维与囊泡谷氨酸转运蛋白 2 共定位。这些数据表明，谷氨酸能神经元代表 PBN 中的一种细胞类型，通过刺激心脏交感神经传入而激活。一氧化氮有可能影响谷氨酸能神经元在调节由心脏交感传入神经激活引起的兴奋性心血管反应中的作用。 (c) 2005 Elsevier B.V. 保留所有权利。
Our previous studies have demonstrated that stimulation of cardiac sympathetic afferents activates neurons in the parabrachial nucleus (PBN), a region known to play a role in central integration of cardiovascular autonomic reflexes. However, phenotypes of these activated neurons have not been well identified. Glutamate, an important excitatory neurotransmitter in the brain, is involved in PBN-mediated cardiovascular responses. Recent identification of vesicular glutamate transporter 3 (VGLUT3) has provided a novel and unique marker to locate distinctive perikarya of neurons that use glutamate as a neurotransmitter. The action of glutamate in the brain is influenced by nitric oxide. Thus, using triple immunofluorescent labeling, the present study examined expression of c-Fos, an immediate early gene, in the neurons containing VGLUT3 and neuronal nitric oxide synthase (nNOS) in the PBN following stimulation of cardiac sympathetic afferents. In anesthetized cats with bilateral barodenervation and cervical vagotomy, topical application of bradykinin (BK, 1-10 mu g/ml, 50 mu l, n = 6) on the left ventricle was performed six times, every 20 min. Repeated administration of BK elicited consistent increases in blood pressure over a 100 min period while no changes were noted in the animals treated with the vehicle for BK (0.9% saline, n = 5). Compared to control cats, c-Fos expression was increased significantly in the cell bodies containing VGLUT3 as well as both VGLUT3 and nNOS in the external lateral PBN (elPBN) in BK-treated animals (all P < 0.01). In addition, using similar triple-staining method, we noted that fibers of activated neurons containing nNOS in the elPBN co-localized with vesicular glutamate transporter 2 following BK stimulation. These data suggest that glutamatergic neurons represent a cell type in the PBN that is activated by stimulation of cardiac sympathetic afferents. Nitric oxide has the potential to influence the action of glutamatergic neurons in regulation of excitatory cardiovascular responses induced by activation of cardiac sympathetic afferents. (c) 2005 Elsevier B.V. All rights reserved.