Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON N6A 5C1, Canada.
Neuroscience. 2013 Oct 10;250:599-613. doi: 10.1016/j.neuroscience.2013.07.054. Epub 2013 Jul 30.
Experiments were done to investigate whether hypothalamic hypocretin-1 (hcrt-1; orexin-A) neurons that sent axonal projections to cardiovascular responsive sites in the nucleus of the solitary tract (NTS) co-expressed leucine-enkephalin (L-Enk), and to determine the effects of co-administration of hcrt-1 and D-Ala2,D-Leu5-Enkephalin (DADL) into NTS on mean arterial pressure (MAP) and heart rate. In the first series, in the Wistar rat the retrograde tract-tracer fluorogold (FG) was microinjected (50nl) into caudal NTS sites at which L-glutamate (0.25 M; 10 nl) elicited decreases in MAP and where fibers hcrt-1 immunoreactive fibers were observed that also contained L-Enk immunoreactivity. Of the number of hypothalamic hcrt-1 immunoreactive neurons identified ipsilateral to the NTS injection site (1207 ± 78), 32.3 ± 2.3% co-expressed L-Enk immunoreactivity and of these, 2.6 ± 1.1% were retrogradely labeled with FG. Hcrt-1/L-Enk neurons projecting to NTS were found mainly within the perifornical region. In the second series, the region of caudal NTS found to contain axons that co-expressed hcrt-1 and L-Enk immunoreactivity was microinjected with a combination of hcrt-1 and DADL in α-chloralose anesthetized Wistar rats. Microinjection of DADL into NTS elicited depressor and bradycardia responses similar to those elicited by microinjection of hcrt-1. An hcrt-1 injection immediately after the DADL injection elicited an almost twofold increase in the magnitude of the depressor and bradycardia responses compared to those elicited by hcrt-1 alone. Prior injections of the non-specific opioid receptor antagonist naloxone or the specific opioid δ-receptor antagonist ICI 154,129 significantly attenuated the cardiovascular responses to the combined hcrt-1-DADL injections. Taken together, these data suggest that activation of hypothalamic-opioidergic neuronal systems contribute to the NTS hcrt-1 induced cardiovascular responses, and that this descending hypothalamo-medullary pathway may represent the anatomical substrate by which hcrt-1/L-Enk neurons function in the coordination of autonomic-cardiovascular responses during different behavioral states.
进行了实验以研究下丘脑食欲肽-1（hcrt-1；orexin-A）神经元是否投射到孤束核（NTS）中对心血管有反应的部位，并共同表达亮氨酸脑啡肽（L-Enk），以及确定将 hcrt-1 和 D-Ala2，D-Leu5-脑啡肽（DADL）共同给药到 NTS 对平均动脉压（MAP）和心率的影响。在第一系列中，在 Wistar 大鼠中，将逆行示踪剂荧光金（FG）（50nl）微注射到 NTS 尾部部位，在该部位，L-谷氨酸（0.25 M；10 nl）引起 MAP 降低，并且观察到含有 L-Enk 免疫反应性纤维的 hcrt-1 免疫反应性纤维。在与 NTS 注射部位同侧识别的下丘脑 hcrt-1 免疫反应性神经元数量（1207 ± 78）中，有 32.3 ± 2.3％共同表达 L-Enk 免疫反应性，其中有 2.6 ± 1.1％被 FG 逆行标记。投射到 NTS 的 hcrt-1/L-Enk 神经元主要位于围绕穹窿的区域内。在第二系列中，在含有共同表达 hcrt-1 和 L-Enk 免疫反应性的轴突的 NTS 尾部区域中，用α-氯醛糖麻醉的 Wistar 大鼠中用 hcrt-1 和 DADL 的组合进行了微注射。将 DADL 微注射到 NTS 中会引起降压和心动过缓反应，类似于单独注射 hcrt-1 时引起的反应。在 DADL 注射后立即注射 hcrt-1 会引起降压和心动过缓反应的幅度比单独注射 hcrt-1 时增加近两倍。先前注射非特异性阿片受体拮抗剂纳洛酮或特异性阿片 δ 受体拮抗剂 ICI 154,129 可显著减轻联合 hcrt-1-DADL 注射引起的心血管反应。综上所述，这些数据表明，下丘脑阿片能神经元系统的激活有助于 NTS hcrt-1 诱导的心血管反应，并且该下行下丘脑-延髓通路可能代表了 hcrt-1/L-Enk 神经元在不同行为状态下协调自主-心血管反应的解剖学基础。
