Loewy A D, Marson L, Parkinson D, Perry M A, Sawyer W B
Brain Res. 1986 Oct 29;386(1-2):313-24. doi: 10.1016/0006-8993(86)90168-x.
The objective of the present study was to analyze the anatomical basis of the A5 depressor response and to test if the putative neurotransmitter noradrenaline is involved in the response. Two approaches were used; one was neuroanatomical and the other was pharmacological. First, the retrograde transport method in which two fluorescent markers (Fast blue and rhodamine microspheres) was used in combination with the indirect immunofluorescence technique to establish that A5 catecholamine neurons project to both the spinal cord and the region of the nucleus tractus solitarii (NTS). Second, we analyzed the effects of 6-hydroxydopamine (6-OHDA) lesions of the spinal cord and/or NTS area on the A5 depressor response. This response was elicited by a 80-nl microinjection of L-glutamate (500 mM) into the A5 region in pentobarbital anesthetized rats; it was characterized by a decrease in blood pressure and heart rate. After destruction of various noradrenergic terminal fields we have found that intraspinal injections of 6-OHDA caused a 30% reduction in the blood pressure component of the A5 depressor response and a transient depression of the bradycardic response. This result suggests that only a small portion of the A5 depressor response depends on the descending A5 spinal pathway. Injections of 6-OHDA into the NTS region caused a transient depression of the A5 depressor response, and by 7-14 days postinjection, the response returned to normal. After combined 6-OHDA injections into the spinal cord and NTS area, the blood pressure and heart rate components of the A5 depressor response were reduced to 80% of the control level at 3 days postinjection. By 14 days, even with severe depletion of noradrenaline in the spinal cord (96%) and a moderate depletion of noradrenaline in the NTS (50%), the A5 response was restored to about 80% of its original magnitude, suggesting some type of functional recovery occurs in this system. Third, the blood pressure decrease elicited by L-glutamate stimulation of the A5 cell group was unaffected by pharmacological blockade of the heart. In addition, this response appeared to be normal in rats that had both their autonomic supply to the heart blocked pharmacologically and their spinal cord noradrenaline levels depleted (14 days after intraspinal 6-OHDA injections). These data suggest that the major A5 depressor response operates mainly by inhibition of the sympathetic outflow involved in control of total peripheral resistance and that this system is controlled by a descending spinal pathway which probably does not use noradrenaline as a neurotransmitter.
本研究的目的是分析A5降压反应的解剖学基础，并测试假定的神经递质去甲肾上腺素是否参与该反应。采用了两种方法：一种是神经解剖学方法，另一种是药理学方法。首先，使用逆行运输法，将两种荧光标记物（快蓝和罗丹明微球）与间接免疫荧光技术结合使用，以确定A5儿茶酚胺能神经元投射到脊髓和孤束核（NTS）区域。其次，我们分析了脊髓和/或NTS区域的6-羟基多巴胺（6-OHDA）损伤对A5降压反应的影响。在戊巴比妥麻醉的大鼠中，通过向A5区域微量注射80 nl L-谷氨酸（500 mM）引发该反应；其特征是血压和心率下降。在破坏各种去甲肾上腺素能终末场后，我们发现脊髓内注射6-OHDA导致A5降压反应的血压成分降低30%，并使心动过缓反应短暂抑制。这一结果表明，A5降压反应中只有一小部分依赖于A5脊髓下行通路。向NTS区域注射6-OHDA导致A5降压反应短暂抑制，注射后7 - 14天，反应恢复正常。在脊髓和NTS区域联合注射6-OHDA后，A5降压反应的血压和心率成分在注射后3天降至对照水平的80%。到14天时，即使脊髓中去甲肾上腺素严重耗竭（96%），NTS中去甲肾上腺素中度耗竭（50%），A5反应仍恢复到其原始幅度的约80%，表明该系统发生了某种类型的功能恢复。第三，L-谷氨酸刺激A5细胞群引起的血压下降不受心脏药理学阻断的影响。此外，在心脏自主神经供应被药理学阻断且脊髓去甲肾上腺素水平耗竭的大鼠（脊髓内注射6-OHDA后14天）中，这种反应似乎正常。这些数据表明，主要的A5降压反应主要通过抑制参与控制总外周阻力的交感神经传出而起作用，并且该系统由可能不使用去甲肾上腺素作为神经递质的脊髓下行通路控制。
