Williams Carole A, Ecay Tom, Reifsteck Angela, Fry Bonnie, Ricketts Brian
Department of Physiology, College of Medicine, East Tennessee State University, P.O. Box 70576, Johnson City, TN 37614, USA.
Brain Res. 2003 Feb 14;963(1-2):26-42. doi: 10.1016/s0006-8993(02)03835-0.
Substance P (SP) is released from the feline nucleus tractus solitarius (NTS) in response to activation of skeletal muscle afferent input. However, there are differing results about SP release from the rostral NTS in response to baroreceptor afferent input. An anti-sense oligonucleotide to feline SP (SP-asODN) was injected directly into the rostral NTS of chloralose-anesthetized cats to determine whether blood pressure or heart rate responses to ergoreceptor activation (muscle contraction) or baroreceptor unloading (carotid artery occlusion) were sensitive to SP knockdown. Control injections included either buffer alone or a scrambled-sequenced oligonucleotide (SP-sODN). Both muscle contractions and carotid occlusions were performed 3, 6 and 12 h after the completion of the oligonucleotide injections. The cardiovascular responses to contractions were significantly attenuated 3 and 6 h after SP-asODN, but not by the injection of the SP-sODN. The cardiovascular responses to contractions returned to control levels 12 h post anti-sense injection. No detectable release of SP (using antibody-coated microprobes) was measured 3 and 6 h after SP-asODN injections and the expression of SP-immunoreactivity (SP-IR) in the NTS was significantly attenuated, as determined by immunohistochemistry procedures. In contrast, neither the injection of SP-asODN nor the s-ODN attenuated the cardiovascular responses to carotid occlusions, or altered the pattern of release of SP from the brainstem. Injection of the SP-sODN did not affect the expression of SP-IR. These results suggest that the SP involved with mediating the peripheral somatomotor signal input to the rostral NTS comes from SP-containing neurons within the NTS. Our results also suggest that SP in the rostral NTS does not play a direct role in mediating the cardiovascular responses to unloading the carotid baroreceptors. We suggest that the SP released during isometric contractions excites an inhibitory pathway modulating baroreceptor input, thus contributing to the increase in mean blood pressure.
P物质（SP）在骨骼肌传入输入被激活时从猫的孤束核（NTS）释放。然而，关于延髓头端NTS对压力感受器传入输入的SP释放存在不同结果。将针对猫SP的反义寡核苷酸（SP-asODN）直接注入水合氯醛麻醉猫的延髓头端NTS，以确定对力感受器激活（肌肉收缩）或压力感受器卸载（颈动脉闭塞）的血压或心率反应是否对SP敲低敏感。对照注射包括单独的缓冲液或乱序寡核苷酸（SP-sODN）。在寡核苷酸注射完成后3、6和12小时进行肌肉收缩和颈动脉闭塞操作。在注射SP-asODN后3和6小时，对收缩的心血管反应显著减弱，但注射SP-sODN则无此现象。反义注射后12小时，对收缩的心血管反应恢复到对照水平。在注射SP-asODN后3和6小时，未检测到SP的释放（使用抗体包被的微探针），并且通过免疫组织化学程序确定，NTS中SP免疫反应性（SP-IR）的表达显著减弱。相反，注射SP-asODN或s-ODN均未减弱对颈动脉闭塞的心血管反应，也未改变脑干中SP的释放模式。注射SP-sODN不影响SP-IR的表达。这些结果表明，参与介导外周躯体运动信号输入到延髓头端NTS的SP来自NTS内含有SP的神经元。我们的结果还表明，延髓头端NTS中的SP在介导对颈动脉压力感受器卸载的心血管反应中不发挥直接作用。我们认为，等长收缩期间释放的SP兴奋了一条调节压力感受器输入的抑制性通路，从而导致平均血压升高。
