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Participation of Fos protein at the nucleus tractus solitarius in inhibitory modulation of baroreceptor reflex response in the rat

Identifieur interne : 001553 ( Istex/Corpus ); précédent : 001552; suivant : 001554

Participation of Fos protein at the nucleus tractus solitarius in inhibitory modulation of baroreceptor reflex response in the rat

Auteurs : Cheng-Dean Shih ; Samuel H. H. Chan ; Julie Y. H. Chan

Source :

RBID : ISTEX:4E54E173712C47ABA6D9E2A5166A31F311508ABC

English descriptors

Abstract

We investigated the physiologic role of Fos protein at the nucleus tractus solitarius (NTS) in the modulation of baroreceptor reflex (BRR) in adult, male Sprague-Dawley rats that were anesthetized and maintained with pentobarbital sodium (40 mg/kg, i.p., with 10 mg/kg/h i.v. infusion supplements). Repeated and scheduled activation of the baroreceptors by transient hypertension induced by i.v. administration of phenylephrine (2.5, 5.0 or 10.0 μg/kg) resulted in a significant increase in Fos-like immunoreactivity (Fos-LI), primarily in the caudal part of the NTS. This increase in Fos-LI in the barosensitive NTS neurons was appreciably reduced by bilateral microinjection into the caudal NTS of an antisense oligonucleotide (20 pmol, 20 nl) designed to target a region of the c-fos mRNA that flanks the initiation codon (5′-129 to 143-3′). The same treatment also discernibly enhanced the BRR response, but elicited no appreciable effect on systemic arterial pressure or heart rate. On the other hand, bilateral application to the NTS of the corresponding sense oligonucleotide (20 pmol, 20 nl) or an antisense cDNA (20 pmol, 20 nl) that targeted a different site of the c-fos-mRNA (5′-135 to 149-3′) was ineffective. These results suggest that expression of the inducible c-fos gene in the NTS may represent an early step in the cascade of intracellular events that leads to long-term inhibitory modulation of baroreflex control of blood pressure.

Url:
DOI: 10.1016/0006-8993(96)00771-8

Links to Exploration step

ISTEX:4E54E173712C47ABA6D9E2A5166A31F311508ABC

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<note type="content">Fig. 1: Representative photomicrographs showing the distribution of Fos-like immunoreactivity (Fos-LI) at the caudal NTS in animals that were subject to repeated and scheduled transient hypertension for 180 min (A), and in animals that additionally received bilateral microinjection into the caudal NTS of a sense oligonucleotide (B) or an antisense cDNA (AS1) targeted against the initiation codon of the c-fos mRNA (C). Panel (D) was taken from the same brain stem section as in (C), and demonstrates the presence of Fos-LI at the caudal ventrolateral medulla. Calibration bar: 100 μm. AP, area postrema; NRL, nucleus reticularis lateralis; NTS, nucleus tractus solitarius; ts, tractus solitarius; X, dorsal motor nucleus of vagus.</note>
<note type="content">Fig. 2: Distribution of Fos-like immunoreactivity in four representative rostral-caudal sections of the NTS in animals that were subject to repeated and scheduled transient hypertension for 180 min (A), and in animals that additionally received bilateral microinjection into the caudal NTS of a sense oligonucleotide (B), or an antisense cDNA targeted against the initiation codon (AS1) (C) or a different region (AS2) (D) of the c-fos mRNA. Each dot represents one Fos-positive nucleus. Numbers indicate the distance to the obex. AP, area postrema; NTS, nucleus tractus solitarius; ts, tractus solitarius; X, dorsal motor nucleus of vagus; XII, hypoglossal nucleus.</note>
<note type="content">Fig. 3: Distribution of Fos-positive neurons at eight rostral-caudal levels of the NTS in animals that were subject to repeated and scheduled transient hypertension for 180 min ([↑ BP], n = 6), and in animals that additionally received bilateral microinjection into the caudal NTS of a sense oligonucleotide (n = 8), or an antisense cDNA targeted against the initiation codon (AS1) (n = 10) or a different region (AS2) (n = 8) of the c-fos mRNA. Animals that received bilateral microinjection into the NTS of aCSF and scheduled i.v. injection of saline (n = 3) served as the volume and vehicle control. Values are presented as mean ± S.E.M. * P < 0.05 vs. aCSF or sham-control group (Fig. 4Fig. 4Distribution of Fos-positive neurons at eight rostral-caudal levels of the NTS in animals that were sacrificed immediately after pentobarbital anesthesia (basal, n = 3), received only continuous i.v. infusion of pentobarbital sodium (20 mg/kg/h) for 180 min (anesthesia, n = 3), subject to surgical preparations and placement in stereotaxic headholder without further experimental procedures (sham, n = 3), or received micro-injection of AS1 oligonucleotide to sites outside the confines of the caudal NTS (non-NTS, n = 5). Values are presented as mean ± S.E.M. * P < 0.05 vs. anesthesia group in the Scheffe analysis.) and +P < 0.05 vs. sense treatment group in the Scheffe analysis.</note>
<note type="content">Fig. 5: Time-course changes in baroreceptor reflex (BRR) response to repeated and scheduled transient hypertension for 180 min ([↑ BP], n = 6), and in animals that additionally received bilateral microinjection into the caudal NTS of a sense oligonucleotide (n = 8), an antisense cDNA targeted against the initiation codon (AS1) (n = 10) or a different region (AS2) (n = 8) of the c-fos mRNA, or AS1 oligonucleotide to sites outside the confines of the caudal NTS (non-NTS, n = 5). Values are presented as mean±S.E.M. * P < 0.05 vs. [↑ BP] group in the Scheffe analysis.</note>
<note type="content">Fig. 6: Time-course changes in mean systemic arterial pressure (MSAP) or heart rate (HR) in animals that received bilateral microinjection into the caudal NTS of a sense (n = 5) or AS1 (n = 6) oligonucleotide. Values are presented as mean ± S.E.M. No significant difference between groups (P > 0.05) in two-way ANOVA with repeated measures.</note>
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<ce:simple-para view="all" id="simple-para.0040">We investigated the physiologic role of Fos protein at the nucleus tractus solitarius (NTS) in the modulation of baroreceptor reflex (BRR) in adult, male Sprague-Dawley rats that were anesthetized and maintained with pentobarbital sodium (40 mg/kg, i.p., with 10 mg/kg/h i.v. infusion supplements). Repeated and scheduled activation of the baroreceptors by transient hypertension induced by i.v. administration of phenylephrine (2.5, 5.0 or 10.0 μg/kg) resulted in a significant increase in Fos-like immunoreactivity (Fos-LI), primarily in the caudal part of the NTS. This increase in Fos-LI in the barosensitive NTS neurons was appreciably reduced by bilateral microinjection into the caudal NTS of an antisense oligonucleotide (20 pmol, 20 nl) designed to target a region of the c-
<ce:italic>fos</ce:italic>
mRNA that flanks the initiation codon (5′-129 to 143-3′). The same treatment also discernibly enhanced the BRR response, but elicited no appreciable effect on systemic arterial pressure or heart rate. On the other hand, bilateral application to the NTS of the corresponding sense oligonucleotide (20 pmol, 20 nl) or an antisense cDNA (20 pmol, 20 nl) that targeted a different site of the c-
<ce:italic>fos</ce:italic>
-mRNA (5′-135 to 149-3′) was ineffective. These results suggest that expression of the inducible c-
<ce:italic>fos</ce:italic>
gene in the NTS may represent an early step in the cascade of intracellular events that leads to long-term inhibitory modulation of baroreflex control of blood pressure.</ce:simple-para>
</ce:abstract-sec>
</ce:abstract>
<ce:keywords class="keyword">
<ce:section-title>Keywords</ce:section-title>
<ce:keyword>
<ce:text>Fos-like immunoreactivity</ce:text>
</ce:keyword>
<ce:keyword>
<ce:text>c-
<ce:italic>fos</ce:italic>
oligonucleotide</ce:text>
</ce:keyword>
<ce:keyword>
<ce:text>Nucleus tractus solitarius</ce:text>
</ce:keyword>
<ce:keyword>
<ce:text>Baroreceptor reflex</ce:text>
</ce:keyword>
<ce:keyword>
<ce:text>Rat</ce:text>
</ce:keyword>
</ce:keywords>
</head>
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<title>Participation of Fos protein at the nucleus tractus solitarius in inhibitory modulation of baroreceptor reflex response in the rat</title>
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<title>Participation of Fos protein at the nucleus tractus solitarius in inhibitory modulation of baroreceptor reflex response in the rat</title>
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<name type="personal">
<namePart type="given">Cheng-Dean</namePart>
<namePart type="family">Shih</namePart>
<affiliation>Institute of Physiology, National Yang-Ming University, Taipei 11221, Taiwan, People's Republic of China</affiliation>
<role>
<roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal">
<namePart type="given">Samuel H.H.</namePart>
<namePart type="family">Chan</namePart>
<affiliation>Center for Neuroscience, National Yang-Ming University, Taipei 11221, Taiwan, People's Republic of China</affiliation>
<role>
<roleTerm type="text">author</roleTerm>
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</name>
<name type="personal">
<namePart type="given">Julie Y.H.</namePart>
<namePart type="family">Chan</namePart>
<affiliation>Department of Medical Research, Veterans General Hospital-Taipei, Taipei 11217, Taiwan, People's Republic of China</affiliation>
<description>Corresponding author. Fax: (886) (2) 8751562.</description>
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<dateIssued encoding="w3cdtf">1996</dateIssued>
<copyrightDate encoding="w3cdtf">1996</copyrightDate>
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<languageTerm type="code" authority="iso639-2b">eng</languageTerm>
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<abstract lang="en">We investigated the physiologic role of Fos protein at the nucleus tractus solitarius (NTS) in the modulation of baroreceptor reflex (BRR) in adult, male Sprague-Dawley rats that were anesthetized and maintained with pentobarbital sodium (40 mg/kg, i.p., with 10 mg/kg/h i.v. infusion supplements). Repeated and scheduled activation of the baroreceptors by transient hypertension induced by i.v. administration of phenylephrine (2.5, 5.0 or 10.0 μg/kg) resulted in a significant increase in Fos-like immunoreactivity (Fos-LI), primarily in the caudal part of the NTS. This increase in Fos-LI in the barosensitive NTS neurons was appreciably reduced by bilateral microinjection into the caudal NTS of an antisense oligonucleotide (20 pmol, 20 nl) designed to target a region of the c-fos mRNA that flanks the initiation codon (5′-129 to 143-3′). The same treatment also discernibly enhanced the BRR response, but elicited no appreciable effect on systemic arterial pressure or heart rate. On the other hand, bilateral application to the NTS of the corresponding sense oligonucleotide (20 pmol, 20 nl) or an antisense cDNA (20 pmol, 20 nl) that targeted a different site of the c-fos-mRNA (5′-135 to 149-3′) was ineffective. These results suggest that expression of the inducible c-fos gene in the NTS may represent an early step in the cascade of intracellular events that leads to long-term inhibitory modulation of baroreflex control of blood pressure.</abstract>
<note type="content">Section title: Research report</note>
<note type="content">Fig. 1: Representative photomicrographs showing the distribution of Fos-like immunoreactivity (Fos-LI) at the caudal NTS in animals that were subject to repeated and scheduled transient hypertension for 180 min (A), and in animals that additionally received bilateral microinjection into the caudal NTS of a sense oligonucleotide (B) or an antisense cDNA (AS1) targeted against the initiation codon of the c-fos mRNA (C). Panel (D) was taken from the same brain stem section as in (C), and demonstrates the presence of Fos-LI at the caudal ventrolateral medulla. Calibration bar: 100 μm. AP, area postrema; NRL, nucleus reticularis lateralis; NTS, nucleus tractus solitarius; ts, tractus solitarius; X, dorsal motor nucleus of vagus.</note>
<note type="content">Fig. 2: Distribution of Fos-like immunoreactivity in four representative rostral-caudal sections of the NTS in animals that were subject to repeated and scheduled transient hypertension for 180 min (A), and in animals that additionally received bilateral microinjection into the caudal NTS of a sense oligonucleotide (B), or an antisense cDNA targeted against the initiation codon (AS1) (C) or a different region (AS2) (D) of the c-fos mRNA. Each dot represents one Fos-positive nucleus. Numbers indicate the distance to the obex. AP, area postrema; NTS, nucleus tractus solitarius; ts, tractus solitarius; X, dorsal motor nucleus of vagus; XII, hypoglossal nucleus.</note>
<note type="content">Fig. 3: Distribution of Fos-positive neurons at eight rostral-caudal levels of the NTS in animals that were subject to repeated and scheduled transient hypertension for 180 min ([↑ BP], n = 6), and in animals that additionally received bilateral microinjection into the caudal NTS of a sense oligonucleotide (n = 8), or an antisense cDNA targeted against the initiation codon (AS1) (n = 10) or a different region (AS2) (n = 8) of the c-fos mRNA. Animals that received bilateral microinjection into the NTS of aCSF and scheduled i.v. injection of saline (n = 3) served as the volume and vehicle control. Values are presented as mean ± S.E.M. * P < 0.05 vs. aCSF or sham-control group (Fig. 4Fig. 4Distribution of Fos-positive neurons at eight rostral-caudal levels of the NTS in animals that were sacrificed immediately after pentobarbital anesthesia (basal, n = 3), received only continuous i.v. infusion of pentobarbital sodium (20 mg/kg/h) for 180 min (anesthesia, n = 3), subject to surgical preparations and placement in stereotaxic headholder without further experimental procedures (sham, n = 3), or received micro-injection of AS1 oligonucleotide to sites outside the confines of the caudal NTS (non-NTS, n = 5). Values are presented as mean ± S.E.M. * P < 0.05 vs. anesthesia group in the Scheffe analysis.) and +P < 0.05 vs. sense treatment group in the Scheffe analysis.</note>
<note type="content">Fig. 5: Time-course changes in baroreceptor reflex (BRR) response to repeated and scheduled transient hypertension for 180 min ([↑ BP], n = 6), and in animals that additionally received bilateral microinjection into the caudal NTS of a sense oligonucleotide (n = 8), an antisense cDNA targeted against the initiation codon (AS1) (n = 10) or a different region (AS2) (n = 8) of the c-fos mRNA, or AS1 oligonucleotide to sites outside the confines of the caudal NTS (non-NTS, n = 5). Values are presented as mean±S.E.M. * P < 0.05 vs. [↑ BP] group in the Scheffe analysis.</note>
<note type="content">Fig. 6: Time-course changes in mean systemic arterial pressure (MSAP) or heart rate (HR) in animals that received bilateral microinjection into the caudal NTS of a sense (n = 5) or AS1 (n = 6) oligonucleotide. Values are presented as mean ± S.E.M. No significant difference between groups (P > 0.05) in two-way ANOVA with repeated measures.</note>
<subject lang="en">
<genre>Keywords</genre>
<topic>Fos-like immunoreactivity</topic>
<topic>c-fos oligonucleotide</topic>
<topic>Nucleus tractus solitarius</topic>
<topic>Baroreceptor reflex</topic>
<topic>Rat</topic>
</subject>
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<title>Brain Research</title>
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<titleInfo type="abbreviated">
<title>BRES</title>
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<genre type="journal">journal</genre>
<originInfo>
<dateIssued encoding="w3cdtf">19961028</dateIssued>
</originInfo>
<identifier type="ISSN">0006-8993</identifier>
<identifier type="PII">S0006-8993(00)X0127-8</identifier>
<part>
<date>19961028</date>
<detail type="volume">
<number>738</number>
<caption>vol.</caption>
</detail>
<detail type="issue">
<number>1</number>
<caption>no.</caption>
</detail>
<extent unit="issue pages">
<start>1</start>
<end>180</end>
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<extent unit="pages">
<start>39</start>
<end>47</end>
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<identifier type="istex">4E54E173712C47ABA6D9E2A5166A31F311508ABC</identifier>
<identifier type="DOI">10.1016/0006-8993(96)00771-8</identifier>
<identifier type="PII">0006-8993(96)00771-8</identifier>
<identifier type="ArticleID">96007718</identifier>
<accessCondition type="use and reproduction" contentType="copyright">©1996 Elsevier Science B.V.</accessCondition>
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