Impaired regulation of neuronal nitric oxide synthase and heart rate during exercise in mice lacking one nNOS allele
We tested the hypothesis that a single allele deletion of neuronal nitric oxide synthase (nNOS) would impair the neural control of heart rate following physical training, and that this phenotype could be restored following targeted gene transfer of nNOS. Voluntary wheel-running (+EX) in heterozygous...
Gespeichert in:
| Veröffentlicht in: | The Journal of physiology 2004-08, Vol.558 (3), p.963-974 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 974 |
|---|---|
| container_issue | 3 |
| container_start_page | 963 |
| container_title | The Journal of physiology |
| container_volume | 558 |
| creator | Danson, E. J. F. Mankia, K. S. Golding, S. Dawson, T. Everatt, L. Cai, S. Channon, K. M. Paterson, D. J. |
| description | We tested the hypothesis that a single allele deletion of neuronal nitric oxide synthase (nNOS) would impair the neural control
of heart rate following physical training, and that this phenotype could be restored following targeted gene transfer of nNOS.
Voluntary wheel-running (+EX) in heterozygous nNOS knockout mice ( nNOS +/â , +EX; n = 52; peak performance 9.1 ± 1.8 km day â1 ) was undertaken and compared to wild-type mice ( n = 38; 9.5 ± 0.8 km day â1 ). In anaesthetized wild-type mice, exercise increased phenylephrine-induced bradycardia by 67% (measured as heart rate change,
in beats per minute, divided by the change in arterial blood pressure, in mmHg) or pulse interval response to phenylephrine
by 52% (measured as interbeat interval change, in milliseconds, divided by the change in blood pressure). Heart rate changes
or interbeat interval changes in response to right vagal nerve stimulation were also enhanced by exercise in wild-type atria
( P < 0.05), whereas both in vivo and in vitro responses to exercise were absent in nNOS +/â mice. nNOS inhibition attenuated heart rate responses to vagal nerve stimulation in all atria ( P < 0.05) and normalized the responses in wild-type, +EX with respect to wild-type with no exercise (âEX) atria. Atrial nNOS
mRNA and protein were increased in wild-type, +EX compared to wild-type, âEX ( P < 0.05), although exercise failed to have any effect in nNOS +/â atria. In vivo nNOS gene transfer using adenoviruses targeted to atrial ganglia enhanced choline acetyltransferaseânNOS co-localization
( P < 0.05) and increased phenylephrine-induced bradycardia in vivo and heart rate responses to vagal nerve stimulation in vitro compared to gene transfer of enhanced green fluorescent protein (eGFP, P < 0.01). This difference was abolished by nNOS inhibition ( P < 0.05). In conclusion, genomic regulation of NO bioavailability from nNOS in cardiac autonomic ganglia in response to training
is dependent on both alleles of the gene. Although basal expression of nNOS is normal, polymorphisms of nNOS may interfere with neural regulation of heart rate following training. Targeted gene transfer
of nNOS can restore this impairment. |
| doi_str_mv | 10.1113/jphysiol.2004.062299 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1665015</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>66766715</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5052-900b47981552100c79c255818401c717e13fb112b9b500335eb3bdf1ab98cc883</originalsourceid><addsrcrecordid>eNqNkU1v1DAQhi0EotvCP0DIJzhl8cRxEl-QUAWlqKJIlLPlOJONi2MvdkKbf0-WLF83pJF8eD9m5IeQZ8C2AMBf3e77OdngtjljxZaVeS7lA7KBopRZVUn-kGwYy_OMVwJOyGlKt4wBZ1I-JicgQIiqlhsyXg57bSO2NOJucnq0wdPQUY9TDF476u0YraHh3rZI0-zHXiek2re0Rx1HGvWItJ2i9TuK9xiNXWTr6WANUqfN14MQPFL_8foz1c6hwyfkUaddwqfH94x8eff25vx9dnV9cXn-5iozgok8k4w1RSXr5dYcGDOVNLkQNdQFA1NBhcC7BiBvZCMY41xgw5u2A93I2pi65mfk9dq7n5oBW4N-jNqpfbSDjrMK2qp_FW97tQvfFZSlYCCWghfHghi-TZhGNdhk0DntMUxJlWW1zE9jsRpNDClF7H4vAaYOuNQvXOqAS624ltjzvw_8EzryWQz1arizDuf_KlU3Hz7xIl-iL9dob3f93YJYreYUjMVxVstPKq5kyfkPUvi0_A</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>66766715</pqid></control><display><type>article</type><title>Impaired regulation of neuronal nitric oxide synthase and heart rate during exercise in mice lacking one nNOS allele</title><source>Wiley Free Content</source><source>MEDLINE</source><source>IngentaConnect Free/Open Access Journals</source><source>Wiley Online Library Journals Frontfile Complete</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Danson, E. J. F. ; Mankia, K. S. ; Golding, S. ; Dawson, T. ; Everatt, L. ; Cai, S. ; Channon, K. M. ; Paterson, D. J.</creator><creatorcontrib>Danson, E. J. F. ; Mankia, K. S. ; Golding, S. ; Dawson, T. ; Everatt, L. ; Cai, S. ; Channon, K. M. ; Paterson, D. J.</creatorcontrib><description><![CDATA[We tested the hypothesis that a single allele deletion of neuronal nitric oxide synthase (nNOS) would impair the neural control
of heart rate following physical training, and that this phenotype could be restored following targeted gene transfer of nNOS.
Voluntary wheel-running (+EX) in heterozygous nNOS knockout mice ( nNOS +/â , +EX; n = 52; peak performance 9.1 ± 1.8 km day â1 ) was undertaken and compared to wild-type mice ( n = 38; 9.5 ± 0.8 km day â1 ). In anaesthetized wild-type mice, exercise increased phenylephrine-induced bradycardia by 67% (measured as heart rate change,
in beats per minute, divided by the change in arterial blood pressure, in mmHg) or pulse interval response to phenylephrine
by 52% (measured as interbeat interval change, in milliseconds, divided by the change in blood pressure). Heart rate changes
or interbeat interval changes in response to right vagal nerve stimulation were also enhanced by exercise in wild-type atria
( P < 0.05), whereas both in vivo and in vitro responses to exercise were absent in nNOS +/â mice. nNOS inhibition attenuated heart rate responses to vagal nerve stimulation in all atria ( P < 0.05) and normalized the responses in wild-type, +EX with respect to wild-type with no exercise (âEX) atria. Atrial nNOS
mRNA and protein were increased in wild-type, +EX compared to wild-type, âEX ( P < 0.05), although exercise failed to have any effect in nNOS +/â atria. In vivo nNOS gene transfer using adenoviruses targeted to atrial ganglia enhanced choline acetyltransferaseânNOS co-localization
( P < 0.05) and increased phenylephrine-induced bradycardia in vivo and heart rate responses to vagal nerve stimulation in vitro compared to gene transfer of enhanced green fluorescent protein (eGFP, P < 0.01). This difference was abolished by nNOS inhibition ( P < 0.05). In conclusion, genomic regulation of NO bioavailability from nNOS in cardiac autonomic ganglia in response to training
is dependent on both alleles of the gene. Although basal expression of nNOS is normal, polymorphisms of nNOS may interfere with neural regulation of heart rate following training. Targeted gene transfer
of nNOS can restore this impairment.]]></description><identifier>ISSN: 0022-3751</identifier><identifier>EISSN: 1469-7793</identifier><identifier>DOI: 10.1113/jphysiol.2004.062299</identifier><identifier>PMID: 15155789</identifier><language>eng</language><publisher>9600 Garsington Road , Oxford , OX4 2DQ , UK: The Physiological Society</publisher><subject>Alleles ; Animals ; Heart Rate - genetics ; Heart Rate - physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nitric Oxide Synthase - deficiency ; Nitric Oxide Synthase - genetics ; Nitric Oxide Synthase - physiology ; Nitric Oxide Synthase Type I ; Physical Conditioning, Animal - physiology ; Research Papers</subject><ispartof>The Journal of physiology, 2004-08, Vol.558 (3), p.963-974</ispartof><rights>2004 The Journal of Physiology © 2004 The Physiological Society</rights><rights>The Physiological Society 2004 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5052-900b47981552100c79c255818401c717e13fb112b9b500335eb3bdf1ab98cc883</citedby><cites>FETCH-LOGICAL-c5052-900b47981552100c79c255818401c717e13fb112b9b500335eb3bdf1ab98cc883</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1665015/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1665015/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,1427,27901,27902,45550,45551,46384,46808,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15155789$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Danson, E. J. F.</creatorcontrib><creatorcontrib>Mankia, K. S.</creatorcontrib><creatorcontrib>Golding, S.</creatorcontrib><creatorcontrib>Dawson, T.</creatorcontrib><creatorcontrib>Everatt, L.</creatorcontrib><creatorcontrib>Cai, S.</creatorcontrib><creatorcontrib>Channon, K. M.</creatorcontrib><creatorcontrib>Paterson, D. J.</creatorcontrib><title>Impaired regulation of neuronal nitric oxide synthase and heart rate during exercise in mice lacking one nNOS allele</title><title>The Journal of physiology</title><addtitle>J Physiol</addtitle><description><![CDATA[We tested the hypothesis that a single allele deletion of neuronal nitric oxide synthase (nNOS) would impair the neural control
of heart rate following physical training, and that this phenotype could be restored following targeted gene transfer of nNOS.
Voluntary wheel-running (+EX) in heterozygous nNOS knockout mice ( nNOS +/â , +EX; n = 52; peak performance 9.1 ± 1.8 km day â1 ) was undertaken and compared to wild-type mice ( n = 38; 9.5 ± 0.8 km day â1 ). In anaesthetized wild-type mice, exercise increased phenylephrine-induced bradycardia by 67% (measured as heart rate change,
in beats per minute, divided by the change in arterial blood pressure, in mmHg) or pulse interval response to phenylephrine
by 52% (measured as interbeat interval change, in milliseconds, divided by the change in blood pressure). Heart rate changes
or interbeat interval changes in response to right vagal nerve stimulation were also enhanced by exercise in wild-type atria
( P < 0.05), whereas both in vivo and in vitro responses to exercise were absent in nNOS +/â mice. nNOS inhibition attenuated heart rate responses to vagal nerve stimulation in all atria ( P < 0.05) and normalized the responses in wild-type, +EX with respect to wild-type with no exercise (âEX) atria. Atrial nNOS
mRNA and protein were increased in wild-type, +EX compared to wild-type, âEX ( P < 0.05), although exercise failed to have any effect in nNOS +/â atria. In vivo nNOS gene transfer using adenoviruses targeted to atrial ganglia enhanced choline acetyltransferaseânNOS co-localization
( P < 0.05) and increased phenylephrine-induced bradycardia in vivo and heart rate responses to vagal nerve stimulation in vitro compared to gene transfer of enhanced green fluorescent protein (eGFP, P < 0.01). This difference was abolished by nNOS inhibition ( P < 0.05). In conclusion, genomic regulation of NO bioavailability from nNOS in cardiac autonomic ganglia in response to training
is dependent on both alleles of the gene. Although basal expression of nNOS is normal, polymorphisms of nNOS may interfere with neural regulation of heart rate following training. Targeted gene transfer
of nNOS can restore this impairment.]]></description><subject>Alleles</subject><subject>Animals</subject><subject>Heart Rate - genetics</subject><subject>Heart Rate - physiology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Nitric Oxide Synthase - deficiency</subject><subject>Nitric Oxide Synthase - genetics</subject><subject>Nitric Oxide Synthase - physiology</subject><subject>Nitric Oxide Synthase Type I</subject><subject>Physical Conditioning, Animal - physiology</subject><subject>Research Papers</subject><issn>0022-3751</issn><issn>1469-7793</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1v1DAQhi0EotvCP0DIJzhl8cRxEl-QUAWlqKJIlLPlOJONi2MvdkKbf0-WLF83pJF8eD9m5IeQZ8C2AMBf3e77OdngtjljxZaVeS7lA7KBopRZVUn-kGwYy_OMVwJOyGlKt4wBZ1I-JicgQIiqlhsyXg57bSO2NOJucnq0wdPQUY9TDF476u0YraHh3rZI0-zHXiek2re0Rx1HGvWItJ2i9TuK9xiNXWTr6WANUqfN14MQPFL_8foz1c6hwyfkUaddwqfH94x8eff25vx9dnV9cXn-5iozgok8k4w1RSXr5dYcGDOVNLkQNdQFA1NBhcC7BiBvZCMY41xgw5u2A93I2pi65mfk9dq7n5oBW4N-jNqpfbSDjrMK2qp_FW97tQvfFZSlYCCWghfHghi-TZhGNdhk0DntMUxJlWW1zE9jsRpNDClF7H4vAaYOuNQvXOqAS624ltjzvw_8EzryWQz1arizDuf_KlU3Hz7xIl-iL9dob3f93YJYreYUjMVxVstPKq5kyfkPUvi0_A</recordid><startdate>200408</startdate><enddate>200408</enddate><creator>Danson, E. J. F.</creator><creator>Mankia, K. S.</creator><creator>Golding, S.</creator><creator>Dawson, T.</creator><creator>Everatt, L.</creator><creator>Cai, S.</creator><creator>Channon, K. M.</creator><creator>Paterson, D. J.</creator><general>The Physiological Society</general><general>Blackwell Science Ltd</general><general>Blackwell Science Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>200408</creationdate><title>Impaired regulation of neuronal nitric oxide synthase and heart rate during exercise in mice lacking one nNOS allele</title><author>Danson, E. J. F. ; Mankia, K. S. ; Golding, S. ; Dawson, T. ; Everatt, L. ; Cai, S. ; Channon, K. M. ; Paterson, D. J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5052-900b47981552100c79c255818401c717e13fb112b9b500335eb3bdf1ab98cc883</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Alleles</topic><topic>Animals</topic><topic>Heart Rate - genetics</topic><topic>Heart Rate - physiology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Nitric Oxide Synthase - deficiency</topic><topic>Nitric Oxide Synthase - genetics</topic><topic>Nitric Oxide Synthase - physiology</topic><topic>Nitric Oxide Synthase Type I</topic><topic>Physical Conditioning, Animal - physiology</topic><topic>Research Papers</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Danson, E. J. F.</creatorcontrib><creatorcontrib>Mankia, K. S.</creatorcontrib><creatorcontrib>Golding, S.</creatorcontrib><creatorcontrib>Dawson, T.</creatorcontrib><creatorcontrib>Everatt, L.</creatorcontrib><creatorcontrib>Cai, S.</creatorcontrib><creatorcontrib>Channon, K. M.</creatorcontrib><creatorcontrib>Paterson, D. J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Danson, E. J. F.</au><au>Mankia, K. S.</au><au>Golding, S.</au><au>Dawson, T.</au><au>Everatt, L.</au><au>Cai, S.</au><au>Channon, K. M.</au><au>Paterson, D. J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impaired regulation of neuronal nitric oxide synthase and heart rate during exercise in mice lacking one nNOS allele</atitle><jtitle>The Journal of physiology</jtitle><addtitle>J Physiol</addtitle><date>2004-08</date><risdate>2004</risdate><volume>558</volume><issue>3</issue><spage>963</spage><epage>974</epage><pages>963-974</pages><issn>0022-3751</issn><eissn>1469-7793</eissn><abstract><![CDATA[We tested the hypothesis that a single allele deletion of neuronal nitric oxide synthase (nNOS) would impair the neural control
of heart rate following physical training, and that this phenotype could be restored following targeted gene transfer of nNOS.
Voluntary wheel-running (+EX) in heterozygous nNOS knockout mice ( nNOS +/â , +EX; n = 52; peak performance 9.1 ± 1.8 km day â1 ) was undertaken and compared to wild-type mice ( n = 38; 9.5 ± 0.8 km day â1 ). In anaesthetized wild-type mice, exercise increased phenylephrine-induced bradycardia by 67% (measured as heart rate change,
in beats per minute, divided by the change in arterial blood pressure, in mmHg) or pulse interval response to phenylephrine
by 52% (measured as interbeat interval change, in milliseconds, divided by the change in blood pressure). Heart rate changes
or interbeat interval changes in response to right vagal nerve stimulation were also enhanced by exercise in wild-type atria
( P < 0.05), whereas both in vivo and in vitro responses to exercise were absent in nNOS +/â mice. nNOS inhibition attenuated heart rate responses to vagal nerve stimulation in all atria ( P < 0.05) and normalized the responses in wild-type, +EX with respect to wild-type with no exercise (âEX) atria. Atrial nNOS
mRNA and protein were increased in wild-type, +EX compared to wild-type, âEX ( P < 0.05), although exercise failed to have any effect in nNOS +/â atria. In vivo nNOS gene transfer using adenoviruses targeted to atrial ganglia enhanced choline acetyltransferaseânNOS co-localization
( P < 0.05) and increased phenylephrine-induced bradycardia in vivo and heart rate responses to vagal nerve stimulation in vitro compared to gene transfer of enhanced green fluorescent protein (eGFP, P < 0.01). This difference was abolished by nNOS inhibition ( P < 0.05). In conclusion, genomic regulation of NO bioavailability from nNOS in cardiac autonomic ganglia in response to training
is dependent on both alleles of the gene. Although basal expression of nNOS is normal, polymorphisms of nNOS may interfere with neural regulation of heart rate following training. Targeted gene transfer
of nNOS can restore this impairment.]]></abstract><cop>9600 Garsington Road , Oxford , OX4 2DQ , UK</cop><pub>The Physiological Society</pub><pmid>15155789</pmid><doi>10.1113/jphysiol.2004.062299</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-3751 |
| ispartof | The Journal of physiology, 2004-08, Vol.558 (3), p.963-974 |
| issn | 0022-3751 1469-7793 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1665015 |
| source | Wiley Free Content; MEDLINE; IngentaConnect Free/Open Access Journals; Wiley Online Library Journals Frontfile Complete; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Alleles Animals Heart Rate - genetics Heart Rate - physiology Mice Mice, Inbred C57BL Mice, Knockout Nitric Oxide Synthase - deficiency Nitric Oxide Synthase - genetics Nitric Oxide Synthase - physiology Nitric Oxide Synthase Type I Physical Conditioning, Animal - physiology Research Papers |
| title | Impaired regulation of neuronal nitric oxide synthase and heart rate during exercise in mice lacking one nNOS allele |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-10T12%3A46%3A27IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Impaired%20regulation%20of%20neuronal%20nitric%20oxide%20synthase%20and%20heart%20rate%20during%20exercise%20in%20mice%20lacking%20one%20nNOS%20allele&rft.jtitle=The%20Journal%20of%20physiology&rft.au=Danson,%20E.%20J.%20F.&rft.date=2004-08&rft.volume=558&rft.issue=3&rft.spage=963&rft.epage=974&rft.pages=963-974&rft.issn=0022-3751&rft.eissn=1469-7793&rft_id=info:doi/10.1113/jphysiol.2004.062299&rft_dat=%3Cproquest_pubme%3E66766715%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=66766715&rft_id=info:pmid/15155789&rfr_iscdi=true |