title: Depressor and tachypneic responses to chemical stimulation of the ventral respiratory group are reduced by ablation of neurokinin-1 receptor-expressing neurons.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, USA. pascal.fries@fcdonders.kun.nl
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Teresa P
authors.initials: TP
authors.lastname: Germanson
authors.forename: Patrice G
authors.initials: PG
authors.lastname: Guyenet
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced; D007022:Hypotension / Q000139:chemically induced; D000922:Immunotoxins / Q000008:administration & dosage / Q000737:chemistry; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008845:Microinjections; D009699:N-Glycosyl Hydrolases; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology; D010940:Plant Proteins / Q000008:administration & dosage / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000819:agonists / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage; D012119:Respiration / Q000187:drug effects; D012143:Respiratory Physiological Phenomena / Q000187:drug effects; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D013373:Substance P / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D000922:Immunotoxins; D010940:Plant Proteins; D018040:Receptors, Neurokinin-1; D011993:Recombinant Fusion Proteins; D054789:Ribosome Inactivating Proteins, Type 1; C454685:SSP-SAP fusion protein, recombinant; D006710:Homocysteine; C007956:homocysteic acid; D013373:Substance P; D009699:N-Glycosyl Hydrolases; D000076985:Saporins