Document Detail


Direct injection of substance P-antisense oligonucleotide into the feline NTS modifies the cardiovascular responses to ergoreceptor but not baroreceptor afferent input.
MedLine Citation:
PMID:  12560109     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Substance P (SP) is released from the feline nucleus tractus solitarius (NTS) in response to activation of skeletal muscle afferent input. However, there are differing results about SP release from the rostral NTS in response to baroreceptor afferent input. An anti-sense oligonucleotide to feline SP (SP-asODN) was injected directly into the rostral NTS of chloralose-anesthetized cats to determine whether blood pressure or heart rate responses to ergoreceptor activation (muscle contraction) or baroreceptor unloading (carotid artery occlusion) were sensitive to SP knockdown. Control injections included either buffer alone or a scrambled-sequenced oligonucleotide (SP-sODN). Both muscle contractions and carotid occlusions were performed 3, 6 and 12 h after the completion of the oligonucleotide injections. The cardiovascular responses to contractions were significantly attenuated 3 and 6 h after SP-asODN, but not by the injection of the SP-sODN. The cardiovascular responses to contractions returned to control levels 12 h post anti-sense injection. No detectable release of SP (using antibody-coated microprobes) was measured 3 and 6 h after SP-asODN injections and the expression of SP-immunoreactivity (SP-IR) in the NTS was significantly attenuated, as determined by immunohistochemistry procedures. In contrast, neither the injection of SP-asODN nor the s-ODN attenuated the cardiovascular responses to carotid occlusions, or altered the pattern of release of SP from the brainstem. Injection of the SP-sODN did not affect the expression of SP-IR. These results suggest that the SP involved with mediating the peripheral somatomotor signal input to the rostral NTS comes from SP-containing neurons within the NTS. Our results also suggest that SP in the rostral NTS does not play a direct role in mediating the cardiovascular responses to unloading the carotid baroreceptors. We suggest that the SP released during isometric contractions excites an inhibitory pathway modulating baroreceptor input, thus contributing to the increase in mean blood pressure.
Authors:
Carole A Williams; Tom Ecay; Angela Reifsteck; Bonnie Fry; Brian Ricketts
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Brain research     Volume:  963     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  2003 Feb 
Date Detail:
Created Date:  2003-01-31     Completed Date:  2003-04-28     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  26-42     Citation Subset:  IM    
Affiliation:
Department of Physiology, College of Medicine, East Tennessee State University, P.O. Box 70576, Johnson City, TN 37614, USA. williams@etsu.edu
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MeSH Terms
Descriptor/Qualifier:
Afferent Pathways / drug effects
Animals
Baroreflex / drug effects,  physiology
Base Sequence
Blood Pressure / drug effects
Cats
Heart Rate / drug effects
Hemodynamics / drug effects,  physiology*
Image Processing, Computer-Assisted
Immunohistochemistry
Mechanoreceptors / drug effects*
Microinjections
Molecular Sequence Data
Oligonucleotides, Antisense / pharmacology*
Pressoreceptors / drug effects*
Protein Precursors / biosynthesis,  metabolism
RNA, Messenger / biosynthesis,  genetics
Signal Transduction / physiology
Solitary Nucleus / drug effects,  physiology*
Stereotaxic Techniques
Substance P / biosynthesis,  physiology*
Tachykinins / antagonists & inhibitors,  biosynthesis,  metabolism
Chemical
Reg. No./Substance:
0/Oligonucleotides, Antisense; 0/Protein Precursors; 0/RNA, Messenger; 0/Tachykinins; 0/preprotachykinin; 33507-63-0/Substance P

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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