DESCENDING NORADRENERGIC PATHWAYS INVOLVED IN THE A5 DEPRESSOR RESPONSE
DESCENDING NORADRENERGIC PATHWAYS INVOLVED IN THE A5 DEPRESSOR RESPONSE
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DOI：
10.1016/0006-8993(86)90168-x
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发表时间：
1986-10-29
期刊：
影响因子：
2.9
通讯作者：
SAWYER, WB
中科院分区：
文献类型：
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作者：
LOEWY, AD;MARSON, L;SAWYER, WB
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了这一反应。使用了两种方法；一种是神经解剖学方法，另一种是药理学方法。首先，用两种荧光标记物(坚蓝微球和罗丹明微球)结合间接免疫荧光技术，建立了A5儿茶酚胺能神经元投射到脊髓和孤束核区的方法。其次，我们分析了6-羟基多巴胺(6-OHDA)损毁脊髓和/或NTS区对A5降压反应的影响。这种反应是在戊巴比妥钠麻醉大鼠的A5区微量注射L谷氨酸(500 MM)引起的，表现为血压和心率的降低。在破坏各种去甲肾上腺素能终末区后，我们发现：(1)脊髓内注射6-OHDA可使A5降压反应的血压成分降低30%，并使心脏减慢反应一过性抑制。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。(2)NTS区注射6-OHDA可引起A5降压反应的一过性抑制，注射后7~14天，A5降压反应恢复正常。(3)脊髓和NTS区联合注射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%。14天时，即使脊髓去甲肾上腺素严重耗竭(96%)，NTS去甲肾上腺素中度耗竭(50%)，A5反应也恢复到原来的80%左右，这表明该系统发生了某种类型的功能恢复。L-谷氨酸刺激A5细胞组引起的血压下降不受心脏药理阻断的影响。此外，在大鼠的心脏自主神经供应被药物阻断，脊髓去甲肾上腺素水平耗尽(脊髓内注射6-OHDA 14天后)的大鼠中，这种反应似乎是正常的。这些数据表明，主要的A5降压反应主要是通过抑制参与控制总外周阻力的交感神经流出来起作用的，该系统受一条下行脊髓通路控制，该通路可能不使用去甲肾上腺素作为神经递质。
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 (1) 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 bradycardiac response. This result suggests that only a small portion of the A5 depressor response depends on the descending A5 spinal pathway. (2) 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. (3) 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.