Inducible Nitric Oxide Synthase Has Divergent Effects on Vascular and Metabolic Function in Obesity
Inducible Nitric Oxide Synthase Has Divergent Effects on Vascular and Metabolic Function in Obesity Brian T. Noronha , Jian-Mei Li , Stephen B. Wheatcroft , Ajay M. Shah and Mark T. Kearney Cardiovascular Division, King’s College London, London, U.K Address correspondence and reprint requests to Dr....
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| Veröffentlicht in: | Diabetes (New York, N.Y.) N.Y.), 2005-04, Vol.54 (4), p.1082-1089 |
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| description | Inducible Nitric Oxide Synthase Has Divergent Effects on Vascular and Metabolic Function in Obesity
Brian T. Noronha ,
Jian-Mei Li ,
Stephen B. Wheatcroft ,
Ajay M. Shah and
Mark T. Kearney
Cardiovascular Division, King’s College London, London, U.K
Address correspondence and reprint requests to Dr. Mark T. Kearney Department of Cardiology, GKT School of Medicine, Bessemer
Road, Denmark Hill, London, SE59PJ, U.K. E-mail: mark.kearney{at}kcl.ac.uk
Abstract
Previous studies have suggested an involvement of inducible nitric oxide synthase (iNOS) in obesity, but the relation, if
any, between this and mechanisms underlying endothelial dysfunction in obesity is unknown. We studied mice fed an obesogenic
high-fat or standard diet for up to 8 weeks. Obesity was associated with elevated blood pressure; resistance to the glucoregulatory
actions of insulin; resistance to the vascular actions of insulin, assessed as the reduction in phenylephrine constrictor
response of aortic rings after insulin preincubation (lean −21.7 ± 11.5 vs. obese 18.2 ± 15.5%; P < 0.05); and evidence of reactive oxygen species (ROS)-dependent vasodilatation in response to acetylcholine in aortic rings
(change in maximal relaxation to acetylcholine after exposure to catalase: lean −2.1 ± 6.0 vs. obese −15.0 ± 3.8%; P = 0.04). Obese mice had increased expression of iNOS in aorta, with evidence of increased vascular NO production, assessed
as the increase in maximal constriction to phenylephrine after iNOS inhibition with 1400W (lean −3.5 ± 9.1 vs. obese 42.1
± 11.2%; P < 0.001). To further address the role of iNOS in obesity-induced vascular and metabolic dysfunction, we studied the effect
of a high-fat diet in iNOS knockout mice (iNOS KO). Obese iNOS KO mice were protected against the development of resistance
to insulin’s glucoregulatory and vascular effects (insulin-dependent reduction in maximal phenylephrine response: obese wild-type
11.2 ± 15.0 vs. obese iNOS KO −20.0 ± 7.7%; P = 0.02). However, obese iNOS KO mice remained hypertensive (124.0 ± 0.7 vs. 114.9 ± 0.5 mmHg; P < 0.01) and had evidence of increased vascular ROS production. Although these data support iNOS as a target to protect against
the adverse effects of obesity on glucoregulation and vascular insulin resistance, iNOS inhibition does not prevent the development
of raised blood pressure or oxidative stress.
DHE, dihydroethidium
eNOS, endothelial NOS
HOMA, homeostatic model assessment
iNOS, inducible NOS
KO, knockout
l-NMMA, |
| doi_str_mv | 10.2337/diabetes.54.4.1082 |
| format | Article |
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Brian T. Noronha ,
Jian-Mei Li ,
Stephen B. Wheatcroft ,
Ajay M. Shah and
Mark T. Kearney
Cardiovascular Division, King’s College London, London, U.K
Address correspondence and reprint requests to Dr. Mark T. Kearney Department of Cardiology, GKT School of Medicine, Bessemer
Road, Denmark Hill, London, SE59PJ, U.K. E-mail: mark.kearney{at}kcl.ac.uk
Abstract
Previous studies have suggested an involvement of inducible nitric oxide synthase (iNOS) in obesity, but the relation, if
any, between this and mechanisms underlying endothelial dysfunction in obesity is unknown. We studied mice fed an obesogenic
high-fat or standard diet for up to 8 weeks. Obesity was associated with elevated blood pressure; resistance to the glucoregulatory
actions of insulin; resistance to the vascular actions of insulin, assessed as the reduction in phenylephrine constrictor
response of aortic rings after insulin preincubation (lean −21.7 ± 11.5 vs. obese 18.2 ± 15.5%; P < 0.05); and evidence of reactive oxygen species (ROS)-dependent vasodilatation in response to acetylcholine in aortic rings
(change in maximal relaxation to acetylcholine after exposure to catalase: lean −2.1 ± 6.0 vs. obese −15.0 ± 3.8%; P = 0.04). Obese mice had increased expression of iNOS in aorta, with evidence of increased vascular NO production, assessed
as the increase in maximal constriction to phenylephrine after iNOS inhibition with 1400W (lean −3.5 ± 9.1 vs. obese 42.1
± 11.2%; P < 0.001). To further address the role of iNOS in obesity-induced vascular and metabolic dysfunction, we studied the effect
of a high-fat diet in iNOS knockout mice (iNOS KO). Obese iNOS KO mice were protected against the development of resistance
to insulin’s glucoregulatory and vascular effects (insulin-dependent reduction in maximal phenylephrine response: obese wild-type
11.2 ± 15.0 vs. obese iNOS KO −20.0 ± 7.7%; P = 0.02). However, obese iNOS KO mice remained hypertensive (124.0 ± 0.7 vs. 114.9 ± 0.5 mmHg; P < 0.01) and had evidence of increased vascular ROS production. Although these data support iNOS as a target to protect against
the adverse effects of obesity on glucoregulation and vascular insulin resistance, iNOS inhibition does not prevent the development
of raised blood pressure or oxidative stress.
DHE, dihydroethidium
eNOS, endothelial NOS
HOMA, homeostatic model assessment
iNOS, inducible NOS
KO, knockout
l-NMMA, NG-monomethyl-l-arginine
nNOS, neuronal NOS
NOS, NO synthase
ROS, reactive oxygen species
SNP, sodium nitroprusside
Footnotes
Accepted January 10, 2005.
Received October 8, 2004.
DIABETES</description><identifier>ISSN: 0012-1797</identifier><identifier>EISSN: 1939-327X</identifier><identifier>DOI: 10.2337/diabetes.54.4.1082</identifier><identifier>PMID: 15793247</identifier><identifier>CODEN: DIAEAZ</identifier><language>eng</language><publisher>United States: American Diabetes Association</publisher><subject>Acetylcholine - physiology ; Animals ; Aorta - physiology ; Atherosclerosis ; Blood pressure ; Blood Vessels - physiopathology ; Causes of ; Coronary vessels ; Cytokines ; Dietary Fats ; Glucose ; Influence ; Insulin resistance ; Male ; Metabolism ; Mice ; Mice, Knockout ; Nitric oxide ; Nitric Oxide Synthase - genetics ; Nitric Oxide Synthase - metabolism ; Nitric Oxide Synthase Type II ; Nitrogen oxide ; Nitrogen oxides ; Obesity ; Obesity - metabolism ; Obesity - physiopathology ; Plasma ; Reactive Oxygen Species ; Vasodilation - physiology</subject><ispartof>Diabetes (New York, N.Y.), 2005-04, Vol.54 (4), p.1082-1089</ispartof><rights>COPYRIGHT 2005 American Diabetes Association</rights><rights>COPYRIGHT 2005 American Diabetes Association</rights><rights>Copyright American Diabetes Association Apr 2005</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c623t-322788530b032f2bc3301e3f6ac7eb5077842e34b8740ca4f12d55407e1a88ae3</citedby><cites>FETCH-LOGICAL-c623t-322788530b032f2bc3301e3f6ac7eb5077842e34b8740ca4f12d55407e1a88ae3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15793247$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Noronha, Brian T</creatorcontrib><creatorcontrib>Li, Jian-Mei</creatorcontrib><creatorcontrib>Wheatcroft, Stephen B</creatorcontrib><creatorcontrib>Shah, Ajay M</creatorcontrib><creatorcontrib>Kearney, Mark T</creatorcontrib><title>Inducible Nitric Oxide Synthase Has Divergent Effects on Vascular and Metabolic Function in Obesity</title><title>Diabetes (New York, N.Y.)</title><addtitle>Diabetes</addtitle><description>Inducible Nitric Oxide Synthase Has Divergent Effects on Vascular and Metabolic Function in Obesity
Brian T. Noronha ,
Jian-Mei Li ,
Stephen B. Wheatcroft ,
Ajay M. Shah and
Mark T. Kearney
Cardiovascular Division, King’s College London, London, U.K
Address correspondence and reprint requests to Dr. Mark T. Kearney Department of Cardiology, GKT School of Medicine, Bessemer
Road, Denmark Hill, London, SE59PJ, U.K. E-mail: mark.kearney{at}kcl.ac.uk
Abstract
Previous studies have suggested an involvement of inducible nitric oxide synthase (iNOS) in obesity, but the relation, if
any, between this and mechanisms underlying endothelial dysfunction in obesity is unknown. We studied mice fed an obesogenic
high-fat or standard diet for up to 8 weeks. Obesity was associated with elevated blood pressure; resistance to the glucoregulatory
actions of insulin; resistance to the vascular actions of insulin, assessed as the reduction in phenylephrine constrictor
response of aortic rings after insulin preincubation (lean −21.7 ± 11.5 vs. obese 18.2 ± 15.5%; P < 0.05); and evidence of reactive oxygen species (ROS)-dependent vasodilatation in response to acetylcholine in aortic rings
(change in maximal relaxation to acetylcholine after exposure to catalase: lean −2.1 ± 6.0 vs. obese −15.0 ± 3.8%; P = 0.04). Obese mice had increased expression of iNOS in aorta, with evidence of increased vascular NO production, assessed
as the increase in maximal constriction to phenylephrine after iNOS inhibition with 1400W (lean −3.5 ± 9.1 vs. obese 42.1
± 11.2%; P < 0.001). To further address the role of iNOS in obesity-induced vascular and metabolic dysfunction, we studied the effect
of a high-fat diet in iNOS knockout mice (iNOS KO). Obese iNOS KO mice were protected against the development of resistance
to insulin’s glucoregulatory and vascular effects (insulin-dependent reduction in maximal phenylephrine response: obese wild-type
11.2 ± 15.0 vs. obese iNOS KO −20.0 ± 7.7%; P = 0.02). However, obese iNOS KO mice remained hypertensive (124.0 ± 0.7 vs. 114.9 ± 0.5 mmHg; P < 0.01) and had evidence of increased vascular ROS production. Although these data support iNOS as a target to protect against
the adverse effects of obesity on glucoregulation and vascular insulin resistance, iNOS inhibition does not prevent the development
of raised blood pressure or oxidative stress.
DHE, dihydroethidium
eNOS, endothelial NOS
HOMA, homeostatic model assessment
iNOS, inducible NOS
KO, knockout
l-NMMA, NG-monomethyl-l-arginine
nNOS, neuronal NOS
NOS, NO synthase
ROS, reactive oxygen species
SNP, sodium nitroprusside
Footnotes
Accepted January 10, 2005.
Received October 8, 2004.
DIABETES</description><subject>Acetylcholine - physiology</subject><subject>Animals</subject><subject>Aorta - physiology</subject><subject>Atherosclerosis</subject><subject>Blood pressure</subject><subject>Blood Vessels - physiopathology</subject><subject>Causes of</subject><subject>Coronary vessels</subject><subject>Cytokines</subject><subject>Dietary Fats</subject><subject>Glucose</subject><subject>Influence</subject><subject>Insulin resistance</subject><subject>Male</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Nitric oxide</subject><subject>Nitric Oxide Synthase - genetics</subject><subject>Nitric Oxide Synthase - metabolism</subject><subject>Nitric Oxide Synthase Type II</subject><subject>Nitrogen oxide</subject><subject>Nitrogen oxides</subject><subject>Obesity</subject><subject>Obesity - metabolism</subject><subject>Obesity - physiopathology</subject><subject>Plasma</subject><subject>Reactive Oxygen Species</subject><subject>Vasodilation - physiology</subject><issn>0012-1797</issn><issn>1939-327X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNptkktrGzEUhYfS0rhp_0AXRXRRCGWmes1IswxuXuDWiz7oTmg0d2wFWZNKmib-91WwS3AxdyHQ_c7hcjhF8ZbgijImPvVWd5AgVjWveEWwpM-KGWlZWzIqfj0vZhgTWhLRipPiVYy3GOMmz8vihNSiZZSLWWFufD8Z2zlAX20K1qDlg-0Bfdv6tNYR0LWO6LP9A2EFPqGLYQCTIho9-qmjmZwOSPsefYGku9Fl-eXkTbJ5bz1adhBt2r4uXgzaRXizf0-LH5cX3-fX5WJ5dTM_X5SmoSzlo6mQsma4w4wOtDOMYQJsaLQR0NVYCMkpMN5JwbHRfCC0r2uOBRAtpQZ2WnzY-d6F8fcEMamNjQac0x7GKapG1A3Nggy-_w-8Hafg822KkoaLVsomQ-UOWmkHyvphTEGbnAIE7UYPg83f54QRRnOubearI3yeHjbWHBWcHQgyk-AhrfQUo5JXi0O2PMaa0TlYgcoxzpeHPN3xJowxBhjUXbAbHbaKYPVYHvWvPKrmiqvH8mTRu30sU7eB_kmyb0sGPu6AtV2t722AJ5cjdn8B0S_NAg</recordid><startdate>20050401</startdate><enddate>20050401</enddate><creator>Noronha, Brian T</creator><creator>Li, Jian-Mei</creator><creator>Wheatcroft, Stephen B</creator><creator>Shah, Ajay M</creator><creator>Kearney, Mark T</creator><general>American Diabetes Association</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>8GL</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope></search><sort><creationdate>20050401</creationdate><title>Inducible Nitric Oxide Synthase Has Divergent Effects on Vascular and Metabolic Function in Obesity</title><author>Noronha, Brian T ; Li, Jian-Mei ; Wheatcroft, Stephen B ; Shah, Ajay M ; Kearney, Mark T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c623t-322788530b032f2bc3301e3f6ac7eb5077842e34b8740ca4f12d55407e1a88ae3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Acetylcholine - physiology</topic><topic>Animals</topic><topic>Aorta - physiology</topic><topic>Atherosclerosis</topic><topic>Blood pressure</topic><topic>Blood Vessels - physiopathology</topic><topic>Causes of</topic><topic>Coronary vessels</topic><topic>Cytokines</topic><topic>Dietary Fats</topic><topic>Glucose</topic><topic>Influence</topic><topic>Insulin resistance</topic><topic>Male</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Nitric oxide</topic><topic>Nitric Oxide Synthase - genetics</topic><topic>Nitric Oxide Synthase - metabolism</topic><topic>Nitric Oxide Synthase Type II</topic><topic>Nitrogen oxide</topic><topic>Nitrogen oxides</topic><topic>Obesity</topic><topic>Obesity - metabolism</topic><topic>Obesity - physiopathology</topic><topic>Plasma</topic><topic>Reactive Oxygen Species</topic><topic>Vasodilation - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Noronha, Brian T</creatorcontrib><creatorcontrib>Li, Jian-Mei</creatorcontrib><creatorcontrib>Wheatcroft, Stephen B</creatorcontrib><creatorcontrib>Shah, Ajay M</creatorcontrib><creatorcontrib>Kearney, Mark T</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: High School</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><jtitle>Diabetes (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Noronha, Brian T</au><au>Li, Jian-Mei</au><au>Wheatcroft, Stephen B</au><au>Shah, Ajay M</au><au>Kearney, Mark T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inducible Nitric Oxide Synthase Has Divergent Effects on Vascular and Metabolic Function in Obesity</atitle><jtitle>Diabetes (New York, N.Y.)</jtitle><addtitle>Diabetes</addtitle><date>2005-04-01</date><risdate>2005</risdate><volume>54</volume><issue>4</issue><spage>1082</spage><epage>1089</epage><pages>1082-1089</pages><issn>0012-1797</issn><eissn>1939-327X</eissn><coden>DIAEAZ</coden><abstract>Inducible Nitric Oxide Synthase Has Divergent Effects on Vascular and Metabolic Function in Obesity
Brian T. Noronha ,
Jian-Mei Li ,
Stephen B. Wheatcroft ,
Ajay M. Shah and
Mark T. Kearney
Cardiovascular Division, King’s College London, London, U.K
Address correspondence and reprint requests to Dr. Mark T. Kearney Department of Cardiology, GKT School of Medicine, Bessemer
Road, Denmark Hill, London, SE59PJ, U.K. E-mail: mark.kearney{at}kcl.ac.uk
Abstract
Previous studies have suggested an involvement of inducible nitric oxide synthase (iNOS) in obesity, but the relation, if
any, between this and mechanisms underlying endothelial dysfunction in obesity is unknown. We studied mice fed an obesogenic
high-fat or standard diet for up to 8 weeks. Obesity was associated with elevated blood pressure; resistance to the glucoregulatory
actions of insulin; resistance to the vascular actions of insulin, assessed as the reduction in phenylephrine constrictor
response of aortic rings after insulin preincubation (lean −21.7 ± 11.5 vs. obese 18.2 ± 15.5%; P < 0.05); and evidence of reactive oxygen species (ROS)-dependent vasodilatation in response to acetylcholine in aortic rings
(change in maximal relaxation to acetylcholine after exposure to catalase: lean −2.1 ± 6.0 vs. obese −15.0 ± 3.8%; P = 0.04). Obese mice had increased expression of iNOS in aorta, with evidence of increased vascular NO production, assessed
as the increase in maximal constriction to phenylephrine after iNOS inhibition with 1400W (lean −3.5 ± 9.1 vs. obese 42.1
± 11.2%; P < 0.001). To further address the role of iNOS in obesity-induced vascular and metabolic dysfunction, we studied the effect
of a high-fat diet in iNOS knockout mice (iNOS KO). Obese iNOS KO mice were protected against the development of resistance
to insulin’s glucoregulatory and vascular effects (insulin-dependent reduction in maximal phenylephrine response: obese wild-type
11.2 ± 15.0 vs. obese iNOS KO −20.0 ± 7.7%; P = 0.02). However, obese iNOS KO mice remained hypertensive (124.0 ± 0.7 vs. 114.9 ± 0.5 mmHg; P < 0.01) and had evidence of increased vascular ROS production. Although these data support iNOS as a target to protect against
the adverse effects of obesity on glucoregulation and vascular insulin resistance, iNOS inhibition does not prevent the development
of raised blood pressure or oxidative stress.
DHE, dihydroethidium
eNOS, endothelial NOS
HOMA, homeostatic model assessment
iNOS, inducible NOS
KO, knockout
l-NMMA, NG-monomethyl-l-arginine
nNOS, neuronal NOS
NOS, NO synthase
ROS, reactive oxygen species
SNP, sodium nitroprusside
Footnotes
Accepted January 10, 2005.
Received October 8, 2004.
DIABETES</abstract><cop>United States</cop><pub>American Diabetes Association</pub><pmid>15793247</pmid><doi>10.2337/diabetes.54.4.1082</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0012-1797 |
| ispartof | Diabetes (New York, N.Y.), 2005-04, Vol.54 (4), p.1082-1089 |
| issn | 0012-1797 1939-327X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_67562540 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Acetylcholine - physiology Animals Aorta - physiology Atherosclerosis Blood pressure Blood Vessels - physiopathology Causes of Coronary vessels Cytokines Dietary Fats Glucose Influence Insulin resistance Male Metabolism Mice Mice, Knockout Nitric oxide Nitric Oxide Synthase - genetics Nitric Oxide Synthase - metabolism Nitric Oxide Synthase Type II Nitrogen oxide Nitrogen oxides Obesity Obesity - metabolism Obesity - physiopathology Plasma Reactive Oxygen Species Vasodilation - physiology |
| title | Inducible Nitric Oxide Synthase Has Divergent Effects on Vascular and Metabolic Function in Obesity |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-22T07%3A13%3A49IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Inducible%20Nitric%20Oxide%20Synthase%20Has%20Divergent%20Effects%20on%20Vascular%20and%20Metabolic%20Function%20in%20Obesity&rft.jtitle=Diabetes%20(New%20York,%20N.Y.)&rft.au=Noronha,%20Brian%20T&rft.date=2005-04-01&rft.volume=54&rft.issue=4&rft.spage=1082&rft.epage=1089&rft.pages=1082-1089&rft.issn=0012-1797&rft.eissn=1939-327X&rft.coden=DIAEAZ&rft_id=info:doi/10.2337/diabetes.54.4.1082&rft_dat=%3Cgale_proqu%3EA131320069%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=216479886&rft_id=info:pmid/15793247&rft_galeid=A131320069&rfr_iscdi=true |