Wang Hong, Weston Matthew C, McQuiston Travis J, Stornetta Ruth L, Guyenet Patrice G
Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA.
Am J Physiol Heart Circ Physiol. 2003 Dec;285(6):H2757-69. doi: 10.1152/ajpheart.00528.2003. Epub 2003 Aug 21.
Intraparenchymal injection of the saporin conjugate [Sar9, Met (O2)11] substance P-saporin (SSP-SAP) into the ventrolateral medulla (VLM) destroys neurokinin-1 receptor-immunoreactivity (NK1R-ir) neurons selectively. This treatment attenuates the hypotension caused by injection of DL-homocysteic acid (DLH) into the caudal VLM (CVLM). Here we ask whether SSP-SAP creates this deficit by destroying the CVLM GABAergic interneurons that mediate the sympathetic baroreflex (baroactivated depressor neurons) or by destroying other VLM neurons. Two weeks after unilateral SSP-SAP treatment (97% loss of VLM NK1R-ir neurons) DLH-induced hypotension and sympathetic tone inhibition were blunted on the lesioned side. Unlesioned or unilaterally lesioned rats received phenylephrine (PE) while awake to identify CVLM baroactivated depressor neurons by the presence of Fos-ir nuclei. Although CVLM Fos-ir cells were not NK1R-ir, their number was reduced approximately 60-70% on the SSP-SAP-injected side. SSP-SAP spared VLM neurons devoid of NK1R-ir, such as the catecholaminergic cells and the precerebellar glutamatergic neurons. In the pre-Bötzinger region of the VLM the toxin killed glutamatergic neurons while sparing glycinergic and GABAergic inhibitory neurons. In the CVLM region approximately 26% of the inhibitory cells were destroyed. In conclusion, the baroactivated depressor neurons of the CVLM do not appear to express NK1Rs but their activity is probably modulated by a population of excitatory NK1R-ir cells located in the VLM. The results also suggest that a region located below the CVLM (subCVLM) may contain an unrelated population of GABAergic depressor neurons that are NK1R-ir but are either not barosensitive or do not express Fos during baroreceptor stimulation.
将皂草素偶联物[Sar9，Met（O2）11]P物质-皂草素（SSP-SAP）脑实质内注射到延髓腹外侧（VLM）可选择性地破坏神经激肽-1受体免疫反应性（NK1R-ir）神经元。这种处理可减轻向尾侧VLM（CVLM）注射DL-高半胱氨酸（DLH）所引起的低血压。在此，我们探讨SSP-SAP造成这种缺陷是通过破坏介导交感压力反射的CVLMγ-氨基丁酸能中间神经元（压力激活的减压神经元）还是通过破坏其他VLM神经元。单侧SSP-SAP处理两周后（VLM中NK1R-ir神经元损失97%），DLH诱导的低血压和交感神经张力抑制在损伤侧减弱。未损伤或单侧损伤的大鼠在清醒时接受去氧肾上腺素（PE），通过Fos-ir核的存在来识别CVLM压力激活的减压神经元。虽然CVLM Fos-ir细胞不是NK1R-ir，但在注射SSP-SAP的一侧其数量减少了约60-70%。SSP-SAP未损伤缺乏NK1R-ir的VLM神经元，如儿茶酚胺能细胞和小脑前谷氨酸能神经元。在VLM的前包钦格复合体区域，毒素杀死了谷氨酸能神经元，同时保留了甘氨酸能和γ-氨基丁酸能抑制性神经元。在CVLM区域，约26%的抑制性细胞被破坏。总之，CVLM的压力激活的减压神经元似乎不表达NK1R，但它们的活动可能受到位于VLM的一群兴奋性NK1R-ir细胞的调节。结果还表明，位于CVLM下方的一个区域（CVLM下方区域）可能含有一群不相关的γ-氨基丁酸能减压神经元，它们是NK1R-ir，但要么对压力不敏感，要么在压力感受器刺激期间不表达Fos。
