Nitroglycerin tolerance in human vessels : Evidence for impaired nitroglycerin bioconversion
The basis for progressive attenuation of the effects of organic nitrates during long-term therapy (nitrate tolerance) remains controversial; proposed mechanisms include impaired nitrate bioconversion resulting in decreased release of nitric oxide (NO) from nitrates and/or increased NO clearance thro...
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| Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 2000-12, Vol.102 (23), p.2810-2815 |
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| container_title | Circulation (New York, N.Y.) |
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| creator | SAGE, Peter R DE LA LANDE, Ivan S STAFFORD, Irene BENNETT, Catherine L PHILLIPOV, George STUBBERFIELD, John HOROWITZ, John D |
| description | The basis for progressive attenuation of the effects of organic nitrates during long-term therapy (nitrate tolerance) remains controversial; proposed mechanisms include impaired nitrate bioconversion resulting in decreased release of nitric oxide (NO) from nitrates and/or increased NO clearance through a reaction with incrementally generated superoxide (O(2)(-)).
Patients undergoing elective coronary artery bypass were randomized to receive 24 hours of intravenously infused nitroglycerin (NTG; nitrate group) or no nitrate therapy (control group). Discarded segments of the internal mammary artery and saphenous vein were used to examine (1) vascular responsiveness to NTG, sodium nitroprusside, and the calcium ionophore A23187; (2) bioconversion of NTG to 1,2- and 1,3-glyceryl dinitrate; and (3) the generation of O(2)(-). Responses to NTG were reduced 3- to 5-fold in vessels from the nitrate group compared with control vessels (P: |
| doi_str_mv | 10.1161/01.CIR.102.23.2810 |
| format | Article |
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Patients undergoing elective coronary artery bypass were randomized to receive 24 hours of intravenously infused nitroglycerin (NTG; nitrate group) or no nitrate therapy (control group). Discarded segments of the internal mammary artery and saphenous vein were used to examine (1) vascular responsiveness to NTG, sodium nitroprusside, and the calcium ionophore A23187; (2) bioconversion of NTG to 1,2- and 1,3-glyceryl dinitrate; and (3) the generation of O(2)(-). Responses to NTG were reduced 3- to 5-fold in vessels from the nitrate group compared with control vessels (P:<0. 01 for both types of segments), whereas responses to sodium nitroprusside and A23187 were unchanged. Tissue content of 1, 2-glyceryl dinitrate was lower (P:=0.012) in the saphenous veins from the nitrate group than in those from the control group. O(2)(-) generation was greater (P:<0.01) in internal mammary artery samples from the nitrate group than in those from the control group. However, incremental O(2)(-) generation induced by an inhibitor of superoxide dismutase did not affect NTG responses.
NTG tolerance in patients with coronary artery disease is nitrate-specific and is associated with evidence of impaired NTG bioconversion. Tolerance was associated with incremental O(2)(-) generation, but short-term elevation of O(2)(-) did not affect NTG responsiveness, suggesting increased NO clearance by O(2)(-) has a minimal contribution to tolerance.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/01.CIR.102.23.2810</identifier><identifier>PMID: 11104737</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Antianginal agents. Coronary vasodilator agents ; Biological and medical sciences ; Blood Vessels - drug effects ; Blood Vessels - metabolism ; Cardiovascular system ; Coronary Disease - drug therapy ; Coronary Disease - metabolism ; Coronary Disease - surgery ; Drug Tolerance ; Female ; Humans ; Infusions, Intravenous ; Male ; Mammary Arteries - drug effects ; Mammary Arteries - metabolism ; Medical sciences ; Middle Aged ; Nitric Oxide - metabolism ; Nitroglycerin - analogs & derivatives ; Nitroglycerin - metabolism ; Nitroglycerin - pharmacokinetics ; Nitroglycerin - pharmacology ; Nitroglycerin - therapeutic use ; Pharmacology. Drug treatments ; Saphenous Vein - drug effects ; Saphenous Vein - metabolism ; Superoxides - metabolism</subject><ispartof>Circulation (New York, N.Y.), 2000-12, Vol.102 (23), p.2810-2815</ispartof><rights>2001 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. Dec 5, 2000</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c348t-a49bb5b668a831cf55e0cd5448f7776a29c95ace20023214c67683ce1cc741bf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,3674,27905,27906</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=810363$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11104737$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SAGE, Peter R</creatorcontrib><creatorcontrib>DE LA LANDE, Ivan S</creatorcontrib><creatorcontrib>STAFFORD, Irene</creatorcontrib><creatorcontrib>BENNETT, Catherine L</creatorcontrib><creatorcontrib>PHILLIPOV, George</creatorcontrib><creatorcontrib>STUBBERFIELD, John</creatorcontrib><creatorcontrib>HOROWITZ, John D</creatorcontrib><title>Nitroglycerin tolerance in human vessels : Evidence for impaired nitroglycerin bioconversion</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>The basis for progressive attenuation of the effects of organic nitrates during long-term therapy (nitrate tolerance) remains controversial; proposed mechanisms include impaired nitrate bioconversion resulting in decreased release of nitric oxide (NO) from nitrates and/or increased NO clearance through a reaction with incrementally generated superoxide (O(2)(-)).
Patients undergoing elective coronary artery bypass were randomized to receive 24 hours of intravenously infused nitroglycerin (NTG; nitrate group) or no nitrate therapy (control group). Discarded segments of the internal mammary artery and saphenous vein were used to examine (1) vascular responsiveness to NTG, sodium nitroprusside, and the calcium ionophore A23187; (2) bioconversion of NTG to 1,2- and 1,3-glyceryl dinitrate; and (3) the generation of O(2)(-). Responses to NTG were reduced 3- to 5-fold in vessels from the nitrate group compared with control vessels (P:<0. 01 for both types of segments), whereas responses to sodium nitroprusside and A23187 were unchanged. Tissue content of 1, 2-glyceryl dinitrate was lower (P:=0.012) in the saphenous veins from the nitrate group than in those from the control group. O(2)(-) generation was greater (P:<0.01) in internal mammary artery samples from the nitrate group than in those from the control group. However, incremental O(2)(-) generation induced by an inhibitor of superoxide dismutase did not affect NTG responses.
NTG tolerance in patients with coronary artery disease is nitrate-specific and is associated with evidence of impaired NTG bioconversion. Tolerance was associated with incremental O(2)(-) generation, but short-term elevation of O(2)(-) did not affect NTG responsiveness, suggesting increased NO clearance by O(2)(-) has a minimal contribution to tolerance.</description><subject>Antianginal agents. Coronary vasodilator agents</subject><subject>Biological and medical sciences</subject><subject>Blood Vessels - drug effects</subject><subject>Blood Vessels - metabolism</subject><subject>Cardiovascular system</subject><subject>Coronary Disease - drug therapy</subject><subject>Coronary Disease - metabolism</subject><subject>Coronary Disease - surgery</subject><subject>Drug Tolerance</subject><subject>Female</subject><subject>Humans</subject><subject>Infusions, Intravenous</subject><subject>Male</subject><subject>Mammary Arteries - drug effects</subject><subject>Mammary Arteries - metabolism</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Nitric Oxide - metabolism</subject><subject>Nitroglycerin - analogs & derivatives</subject><subject>Nitroglycerin - metabolism</subject><subject>Nitroglycerin - pharmacokinetics</subject><subject>Nitroglycerin - pharmacology</subject><subject>Nitroglycerin - therapeutic use</subject><subject>Pharmacology. Drug treatments</subject><subject>Saphenous Vein - drug effects</subject><subject>Saphenous Vein - metabolism</subject><subject>Superoxides - metabolism</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkE1r3DAQhkVpaDZJ_0APxbSQm12NPu3eyrL5gJBASW4BIWvHrYJtbaX1wv77yGRpSE7DyzzzMjyEfAFaASj4QaFaXv-ugLKK8YrVQD-QBUgmSiF585EsKKVNqTljx-QkpaccFdfyEzkGACo01wvyeOu3Mfzp9w6jH4tt6DHa0WGRw99psGOxw5SwT8XPYrXza5x3XYiFHzbWR1wX45uC1gcXxh3G5MN4Ro462yf8fJin5OFidb-8Km_uLq-Xv25Kx0W9La1o2la2StW25uA6KZG6tRSi7rTWyrLGNdI6ZJQyzkA4pVXNHYJzWkDb8VNy_tK7ieHfhGlrBp8c9r0dMUzJaCaUgoZn8Ns78ClMccy_GQYsPyBqmSH2ArkYUorYmU30g417A9TM4g0Fk8XnyAzjZhafj74emqd2wPXrycF0Br4fAJuc7bvZsk__ublDcf4MiAmLMA</recordid><startdate>20001205</startdate><enddate>20001205</enddate><creator>SAGE, Peter R</creator><creator>DE LA LANDE, Ivan S</creator><creator>STAFFORD, Irene</creator><creator>BENNETT, Catherine L</creator><creator>PHILLIPOV, George</creator><creator>STUBBERFIELD, John</creator><creator>HOROWITZ, John D</creator><general>Lippincott Williams & Wilkins</general><general>American Heart Association, Inc</general><scope>IQODW</scope><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>K9.</scope><scope>NAPCQ</scope><scope>U9A</scope><scope>7X8</scope></search><sort><creationdate>20001205</creationdate><title>Nitroglycerin tolerance in human vessels : Evidence for impaired nitroglycerin bioconversion</title><author>SAGE, Peter R ; DE LA LANDE, Ivan S ; STAFFORD, Irene ; BENNETT, Catherine L ; PHILLIPOV, George ; STUBBERFIELD, John ; HOROWITZ, John D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c348t-a49bb5b668a831cf55e0cd5448f7776a29c95ace20023214c67683ce1cc741bf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Antianginal agents. Coronary vasodilator agents</topic><topic>Biological and medical sciences</topic><topic>Blood Vessels - drug effects</topic><topic>Blood Vessels - metabolism</topic><topic>Cardiovascular system</topic><topic>Coronary Disease - drug therapy</topic><topic>Coronary Disease - metabolism</topic><topic>Coronary Disease - surgery</topic><topic>Drug Tolerance</topic><topic>Female</topic><topic>Humans</topic><topic>Infusions, Intravenous</topic><topic>Male</topic><topic>Mammary Arteries - drug effects</topic><topic>Mammary Arteries - metabolism</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Nitric Oxide - metabolism</topic><topic>Nitroglycerin - analogs & derivatives</topic><topic>Nitroglycerin - metabolism</topic><topic>Nitroglycerin - pharmacokinetics</topic><topic>Nitroglycerin - pharmacology</topic><topic>Nitroglycerin - therapeutic use</topic><topic>Pharmacology. Drug treatments</topic><topic>Saphenous Vein - drug effects</topic><topic>Saphenous Vein - metabolism</topic><topic>Superoxides - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SAGE, Peter R</creatorcontrib><creatorcontrib>DE LA LANDE, Ivan S</creatorcontrib><creatorcontrib>STAFFORD, Irene</creatorcontrib><creatorcontrib>BENNETT, Catherine L</creatorcontrib><creatorcontrib>PHILLIPOV, George</creatorcontrib><creatorcontrib>STUBBERFIELD, John</creatorcontrib><creatorcontrib>HOROWITZ, John D</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SAGE, Peter R</au><au>DE LA LANDE, Ivan S</au><au>STAFFORD, Irene</au><au>BENNETT, Catherine L</au><au>PHILLIPOV, George</au><au>STUBBERFIELD, John</au><au>HOROWITZ, John D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nitroglycerin tolerance in human vessels : Evidence for impaired nitroglycerin bioconversion</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2000-12-05</date><risdate>2000</risdate><volume>102</volume><issue>23</issue><spage>2810</spage><epage>2815</epage><pages>2810-2815</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>The basis for progressive attenuation of the effects of organic nitrates during long-term therapy (nitrate tolerance) remains controversial; proposed mechanisms include impaired nitrate bioconversion resulting in decreased release of nitric oxide (NO) from nitrates and/or increased NO clearance through a reaction with incrementally generated superoxide (O(2)(-)).
Patients undergoing elective coronary artery bypass were randomized to receive 24 hours of intravenously infused nitroglycerin (NTG; nitrate group) or no nitrate therapy (control group). Discarded segments of the internal mammary artery and saphenous vein were used to examine (1) vascular responsiveness to NTG, sodium nitroprusside, and the calcium ionophore A23187; (2) bioconversion of NTG to 1,2- and 1,3-glyceryl dinitrate; and (3) the generation of O(2)(-). Responses to NTG were reduced 3- to 5-fold in vessels from the nitrate group compared with control vessels (P:<0. 01 for both types of segments), whereas responses to sodium nitroprusside and A23187 were unchanged. Tissue content of 1, 2-glyceryl dinitrate was lower (P:=0.012) in the saphenous veins from the nitrate group than in those from the control group. O(2)(-) generation was greater (P:<0.01) in internal mammary artery samples from the nitrate group than in those from the control group. However, incremental O(2)(-) generation induced by an inhibitor of superoxide dismutase did not affect NTG responses.
NTG tolerance in patients with coronary artery disease is nitrate-specific and is associated with evidence of impaired NTG bioconversion. Tolerance was associated with incremental O(2)(-) generation, but short-term elevation of O(2)(-) did not affect NTG responsiveness, suggesting increased NO clearance by O(2)(-) has a minimal contribution to tolerance.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>11104737</pmid><doi>10.1161/01.CIR.102.23.2810</doi><tpages>6</tpages></addata></record> |
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| identifier | ISSN: 0009-7322 |
| ispartof | Circulation (New York, N.Y.), 2000-12, Vol.102 (23), p.2810-2815 |
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| source | MEDLINE; American Heart Association Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Ovid Autoload |
| subjects | Antianginal agents. Coronary vasodilator agents Biological and medical sciences Blood Vessels - drug effects Blood Vessels - metabolism Cardiovascular system Coronary Disease - drug therapy Coronary Disease - metabolism Coronary Disease - surgery Drug Tolerance Female Humans Infusions, Intravenous Male Mammary Arteries - drug effects Mammary Arteries - metabolism Medical sciences Middle Aged Nitric Oxide - metabolism Nitroglycerin - analogs & derivatives Nitroglycerin - metabolism Nitroglycerin - pharmacokinetics Nitroglycerin - pharmacology Nitroglycerin - therapeutic use Pharmacology. Drug treatments Saphenous Vein - drug effects Saphenous Vein - metabolism Superoxides - metabolism |
| title | Nitroglycerin tolerance in human vessels : Evidence for impaired nitroglycerin bioconversion |
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