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The Journal of Neuroscience, May 1, 2002, 22(9):3755-3764
Depressor and Tachypneic Responses to Chemical Stimulation of the Ventral Respiratory Group Are Reduced by Ablation of Neurokinin-1 Receptor-Expressing Neurons
Hong Wang, Teresa P. Germanson, and Patrice G. Guyenet Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908
Our goal was to investigate whether the neurokinin-1 receptor (NK1R)-expressing cells of the rostral ventrolateral medulla (RVLM) regulate respiration and arterial pressure (AP). We examined the consequences of their ablation on the cardiorespiratory responses [phrenic nerve discharge (PND) and AP] caused by injecting DL-homocysteic acid (DLH) into the ventral respiratory group (VRG). In intact rats, DLH produced tachypnea only when injected into the pre-Bötzinger complex (pre-BötC). Injections into pre-BötC and rostral VRG (rVRG) caused hypotension, whereas injections into the Bötzinger region elevated AP. Selective unilateral ablation of RVLM NK1R-immunoreactive cells (97% loss within the pre-BötC and rVRG without loss of catecholaminergic neurons) was done by injecting saporin (SAP) conjugated with a selective NK1R agonist [Sar9, Met(O2)11]-substance P (SSP). Free SAP produced no lesion. Resting AP was normal in SAP- and SSP-SAP-treated rats, but the PND rate was slightly elevated in SSP-SAP-treated rats. The response of SAP-treated rats to DLH injection into VRG was normal and identical on each side, but tachypnea could not be elicited in the pre-BötC of SSP-SAP-treated rats on the toxin-injected side, and DLH caused a long-lasting apnea on the untreated side. The hypotension produced by DLH injection into pre-BötC and rVRG of SSP-SAP-treated rats was reduced on the lesioned side only.
In conclusion, NK1R-expressing cells of the rostral ventrolateral medulla control both respiratory rhythm and blood pressure. However, there is no evidence yet that these two functions are regulated by the same NK1R-expressing neurons.
Key words: substance P; Bötzinger; pre-Bötzinger complex; respiratory rhythm generation; blood pressure; saporin
Copyright © 2002 Society for Neuroscience 0270-6474/02/2293755-10$05.00/0
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