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This Article Full Text Full Text (PDF) All Versions of this Article: 285/6/H2757    most recent 00528.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Wang, H. Articles by Guyenet, P. G. Search for Related Content PubMed PubMed Citation Articles by Wang, H. Articles by Guyenet, P. G.

Neurokinin-1 receptor-expressing cells regulate depressor region of rat ventrolateral medulla

Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908

Submitted 6 June 2003 ; accepted in final form 18 August 2003

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 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 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.

sympathetic tone; blood pressure; respiration; pre-Bötzinger complex; respiratory rhythm generation; substance P; saporin

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