title: Targeted deletion of neurokinin-1 receptor expressing nucleus tractus solitarii neurons precludes somatosensory depression of arterial baroreceptor-heart rate reflex.
abstract: Neurokinin-1 receptor (NK1-R) expressing neurons are densely distributed throughout the nucleus tractus solitarii (NTS). However, their fundamental role in arterial baroreflex function remains debated. Previously, our group has shown that activation of contraction-sensitive somatic afferents evoke substance P (SP) release in the NTS and resets the arterial baroreflex via activation of a GABAergic NTS circuit. Based on these findings, we hypothesized that modulation of arterial baroreflex function by somatic afferents is mediated by NK1-R dependent inhibition of barosensitive NTS circuits. In the present study, SP-conjugated saporin toxin (SP-SAP) was used to ablate NK1-R expressing NTS neurons. Contraction-sensitive somatic afferents were activated by electrically-evoked muscle contraction and the arterial baroreceptor-heart rate reflex was assessed by constructing reflex curves using a decerebrate, arterially-perfused preparation. Baseline baroreflex sensitivity was significantly attenuated in SP-SAP-treated rats compared with control rats receiving either unconjugated SAP or vehicle. Muscle contraction significantly attenuated baroslope in SAP and vehicle-treated animals and shifted the baroreflex curves to higher systemic pressure. In contrast, somatic afferent stimulation failed to alter baroslope or shift the baroreflex curves in SP-SAP-treated animals. Moreover, when reflex sensitivity was partially restored in SP-SAP animals, somatic stimulation failed to attenuate baroreflex bradycardia. In contrast, SP-SAP and somatic stimulation failed to blunt the reflex bradycardia evoked by the peripheral chemoreflex. Immunohistochemistry revealed that pretreatment with SP-SAP significantly reduced the number of NK1-R expressing neurons in the caudal NTS, while sparing NK1-R expressing neurons rostral to the injection site. This was accompanied by a significant reduction in the number of glutamic acid decarboxylase (GAD67) expressing neurons at equivalent levels of the NTS. These findings indicate that immunolesioning of NK1-R expressing NTS neurons selectively abolishes the depressive effect of somatosensory input on arterial baroreceptor-heart rate reflex function.
authors.affiliation: Department of Biomedical Science, College of Veterinary Medicine, Dalton Cardiovascular Research Center, University of Missouri, 134 Research Park Drive, Columbia, MO 65211, USA. pottsjt@missouri.edu <pottsjt@missouri.edu>
authors.forename: J T
authors.initials: JT
authors.lastname: Potts
authors.forename: A Y
authors.initials: AY
authors.lastname: Fong
authors.forename: P I
authors.initials: PI
authors.lastname: Anguelov
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.forename: D
authors.initials: D
authors.lastname: McGovern
authors.forename: I
authors.initials: I
authors.lastname: Grias
mesh_terms: D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D017704:Baroreflex / Q000502:physiology*; D001794:Blood Pressure; D003326:Coronary Circulation / Q000502:physiology; D006321:Heart / Q000502:physiology*; D006339:Heart Rate; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D011311:Pressoreceptors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D017552:Solitary Nucleus / Q000502:physiology*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D018040:Receptors, Neurokinin-1; D054789:Ribosome Inactivating Proteins, Type 1; C468274:substance P-saporin; D013373:Substance P; D000076985:Saporins