Nitric oxide‐ and nitric oxide donors‐induced relaxation and its modulation by oxidative stress in piglet pulmonary arteries
Inhaled nitric oxide (iNO) is widely used in the treatment of pulmonary hypertension while inhaled NO donors have been suggested as an alternative therapy. The differential susceptibility to inactivation by oxidative stress and oxyhaemoglobin of NO and two NO donors, sodium nitroprusside (SNP) and S...
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description | Inhaled nitric oxide (iNO) is widely used in the treatment of pulmonary hypertension while inhaled NO donors have been suggested as an alternative therapy. The differential susceptibility to inactivation by oxidative stress and oxyhaemoglobin of NO and two NO donors, sodium nitroprusside (SNP) and S‐nitroso‐N‐acetyl‐penicillamine (SNAP) were analysed in isolated endothelium‐denuded pulmonary arteries from 2‐week‐old piglets stimulated with U46619.
NO, SNAP and SNP relaxed the arteries (pIC30=7.73±0.12, 7.26±0.17 and 6.43±0.13, respectively) but NO was not detected electrochemically in the bath after the addition of SNP and only at concentrations at which SNAP produced more than 50% relaxation.
The sGC inhibitor ODQ (10−6 M) or the sarcoplasmic Ca2+‐ATPase thapsigargin (2×10−6 M) markedly inhibited the relaxation induced by NO, SNAP and SNP.
Addition of oxyhaemoglobin (3×10−7 M) or diethyldithiocarbamate (1 mM) markedly inhibited NO‐ (pIC30=6.88±0.07 and 6.92±0.18, respectively), weakly inhibited SNAP‐ and had no effect on SNP‐induced relaxation. Xanthine oxidase (5 mu ml−1) plus hypoxanthine (10−4 M) markedly inhibited NO‐ (pIC30=6.96±0.12) but not SNAP‐ or SNP‐induced relaxation.
Superoxide dismutase (SOD), MnCl2, diphenileneiodonium and exposing the luminal surface of the rings outwards (inversion) potentiated the relaxant responses of NO (pIC30=8.52±0.16, 8.23±0.11, 8.01±0.11 and 8.20±0.10, respectively). However, SOD did not modify the NO detected by the electrode and had no effect on SNAP‐ or SNP‐induced relaxation.
Therefore, the kinetics and local distribution of NO release of NO donors influence the susceptibility to the scavenging effects of oxyhaemoglobin and superoxide.
British Journal of Pharmacology (2001) 133, 615–624; doi:10.1038/sj.bjp.0704103 |
doi_str_mv | 10.1038/sj.bjp.0704103 |
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NO, SNAP and SNP relaxed the arteries (pIC30=7.73±0.12, 7.26±0.17 and 6.43±0.13, respectively) but NO was not detected electrochemically in the bath after the addition of SNP and only at concentrations at which SNAP produced more than 50% relaxation.
The sGC inhibitor ODQ (10−6 M) or the sarcoplasmic Ca2+‐ATPase thapsigargin (2×10−6 M) markedly inhibited the relaxation induced by NO, SNAP and SNP.
Addition of oxyhaemoglobin (3×10−7 M) or diethyldithiocarbamate (1 mM) markedly inhibited NO‐ (pIC30=6.88±0.07 and 6.92±0.18, respectively), weakly inhibited SNAP‐ and had no effect on SNP‐induced relaxation. Xanthine oxidase (5 mu ml−1) plus hypoxanthine (10−4 M) markedly inhibited NO‐ (pIC30=6.96±0.12) but not SNAP‐ or SNP‐induced relaxation.
Superoxide dismutase (SOD), MnCl2, diphenileneiodonium and exposing the luminal surface of the rings outwards (inversion) potentiated the relaxant responses of NO (pIC30=8.52±0.16, 8.23±0.11, 8.01±0.11 and 8.20±0.10, respectively). However, SOD did not modify the NO detected by the electrode and had no effect on SNAP‐ or SNP‐induced relaxation.
Therefore, the kinetics and local distribution of NO release of NO donors influence the susceptibility to the scavenging effects of oxyhaemoglobin and superoxide.
British Journal of Pharmacology (2001) 133, 615–624; doi:10.1038/sj.bjp.0704103</description><identifier>ISSN: 0007-1188</identifier><identifier>EISSN: 1476-5381</identifier><identifier>DOI: 10.1038/sj.bjp.0704103</identifier><identifier>PMID: 11429384</identifier><identifier>CODEN: BJPCBM</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Animals ; Biological and medical sciences ; Cardiovascular system ; Dose-Response Relationship, Drug ; Electrochemistry ; Free Radical Scavengers - pharmacology ; In Vitro Techniques ; Male ; Medical sciences ; Nitric Oxide - pharmacology ; Nitric Oxide Donors - pharmacology ; Nitroprusside - pharmacology ; Oxidative Stress ; Oxyhemoglobins - pharmacology ; Penicillamine - analogs & derivatives ; Penicillamine - pharmacology ; Pharmacology. Drug treatments ; piglet ; pulmonary artery ; Pulmonary Artery - drug effects ; Pulmonary Artery - physiology ; SNAP ; Sodium nitroprusside ; superoxide ; Superoxide Dismutase - pharmacology ; Superoxides - metabolism ; Swine ; Swine, Miniature ; Vasodilation - drug effects ; Vasodilator agents. Cerebral vasodilators</subject><ispartof>British journal of pharmacology, 2001-07, Vol.133 (5), p.615-624</ispartof><rights>2001 British Pharmacological Society</rights><rights>2001 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Jul 2001</rights><rights>Copyright 2001, Nature Publishing Group 2001 Nature Publishing Group</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5525-7ea02cbee8a6adb2a9e82add03276a8d09d0628d20e3ec6263362bcff2de76d73</citedby><cites>FETCH-LOGICAL-c5525-7ea02cbee8a6adb2a9e82add03276a8d09d0628d20e3ec6263362bcff2de76d73</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/PMC1572823/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1572823/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,1427,27903,27904,45553,45554,46387,46811,53769,53771</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1066351$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11429384$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>López‐López, José Gustavo</creatorcontrib><creatorcontrib>Pérez‐Vizcaíno, Francisco</creatorcontrib><creatorcontrib>Cogolludo, Angel L</creatorcontrib><creatorcontrib>Ibarra, Manuel</creatorcontrib><creatorcontrib>Zaragozá‐Arnáez, Francisco</creatorcontrib><creatorcontrib>Tamargo, Juan</creatorcontrib><title>Nitric oxide‐ and nitric oxide donors‐induced relaxation and its modulation by oxidative stress in piglet pulmonary arteries</title><title>British journal of pharmacology</title><addtitle>Br J Pharmacol</addtitle><description>Inhaled nitric oxide (iNO) is widely used in the treatment of pulmonary hypertension while inhaled NO donors have been suggested as an alternative therapy. The differential susceptibility to inactivation by oxidative stress and oxyhaemoglobin of NO and two NO donors, sodium nitroprusside (SNP) and S‐nitroso‐N‐acetyl‐penicillamine (SNAP) were analysed in isolated endothelium‐denuded pulmonary arteries from 2‐week‐old piglets stimulated with U46619.
NO, SNAP and SNP relaxed the arteries (pIC30=7.73±0.12, 7.26±0.17 and 6.43±0.13, respectively) but NO was not detected electrochemically in the bath after the addition of SNP and only at concentrations at which SNAP produced more than 50% relaxation.
The sGC inhibitor ODQ (10−6 M) or the sarcoplasmic Ca2+‐ATPase thapsigargin (2×10−6 M) markedly inhibited the relaxation induced by NO, SNAP and SNP.
Addition of oxyhaemoglobin (3×10−7 M) or diethyldithiocarbamate (1 mM) markedly inhibited NO‐ (pIC30=6.88±0.07 and 6.92±0.18, respectively), weakly inhibited SNAP‐ and had no effect on SNP‐induced relaxation. Xanthine oxidase (5 mu ml−1) plus hypoxanthine (10−4 M) markedly inhibited NO‐ (pIC30=6.96±0.12) but not SNAP‐ or SNP‐induced relaxation.
Superoxide dismutase (SOD), MnCl2, diphenileneiodonium and exposing the luminal surface of the rings outwards (inversion) potentiated the relaxant responses of NO (pIC30=8.52±0.16, 8.23±0.11, 8.01±0.11 and 8.20±0.10, respectively). However, SOD did not modify the NO detected by the electrode and had no effect on SNAP‐ or SNP‐induced relaxation.
Therefore, the kinetics and local distribution of NO release of NO donors influence the susceptibility to the scavenging effects of oxyhaemoglobin and superoxide.
British Journal of Pharmacology (2001) 133, 615–624; doi:10.1038/sj.bjp.0704103</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cardiovascular system</subject><subject>Dose-Response Relationship, Drug</subject><subject>Electrochemistry</subject><subject>Free Radical Scavengers - pharmacology</subject><subject>In Vitro Techniques</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Nitric Oxide - pharmacology</subject><subject>Nitric Oxide Donors - pharmacology</subject><subject>Nitroprusside - pharmacology</subject><subject>Oxidative Stress</subject><subject>Oxyhemoglobins - pharmacology</subject><subject>Penicillamine - analogs & derivatives</subject><subject>Penicillamine - pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>piglet</subject><subject>pulmonary artery</subject><subject>Pulmonary Artery - drug effects</subject><subject>Pulmonary Artery - physiology</subject><subject>SNAP</subject><subject>Sodium nitroprusside</subject><subject>superoxide</subject><subject>Superoxide Dismutase - pharmacology</subject><subject>Superoxides - metabolism</subject><subject>Swine</subject><subject>Swine, Miniature</subject><subject>Vasodilation - drug effects</subject><subject>Vasodilator agents. Cerebral vasodilators</subject><issn>0007-1188</issn><issn>1476-5381</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkc9u1DAQxiMEokvhyhFZCHHL4j-J7b0gQQUUqQIOcLYce1Icee1gJ6V76yPwjDwJ3m4ECxdO1sz85pvP-qrqMcFrgpl8kYd1N4xrLHBT6jvVijSC1y2T5G61whiLmhApT6oHOQ8Yl6Fo71cnhDR0w2Szqm4-uCk5g-K1s_Dz5gfSwaJw1EM2hphyGblgZwMWJfD6Wk8uhlvYTRlto539odXtbvdKcQUoTwlyRi6g0V16mNA4-20MOu2QThMkB_lhda_XPsOj5T2tvrx98_nsvL74-O792auL2rQtbWsBGlPTAUjNte2o3oCk2lrMqOBaWryxmFNpKQYGhlPOGKed6XtqQXAr2Gn18qA7zt0WrIEwJe3VmNy22FFRO_X3JLiv6jJeKdIKKikrAs8XgRS_zZAntXXZgPc6QJyzEngjOMGkgE__AYc4p1A-pygRRDYC7-2sD5BJMecE_W8nBKt9sioPqiSrlmTLwpNj_3_wJcoCPFsAnY32fdLBuHwkyzlr9-7YAfvuPOz-c1W9_nROSduyXyYgwtc</recordid><startdate>200107</startdate><enddate>200107</enddate><creator>López‐López, José Gustavo</creator><creator>Pérez‐Vizcaíno, Francisco</creator><creator>Cogolludo, Angel L</creator><creator>Ibarra, Manuel</creator><creator>Zaragozá‐Arnáez, Francisco</creator><creator>Tamargo, Juan</creator><general>Blackwell Publishing Ltd</general><general>Nature Publishing</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>3V.</scope><scope>7QP</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>200107</creationdate><title>Nitric oxide‐ and nitric oxide donors‐induced relaxation and its modulation by oxidative stress in piglet pulmonary arteries</title><author>López‐López, José Gustavo ; Pérez‐Vizcaíno, Francisco ; Cogolludo, Angel L ; Ibarra, Manuel ; Zaragozá‐Arnáez, Francisco ; Tamargo, Juan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5525-7ea02cbee8a6adb2a9e82add03276a8d09d0628d20e3ec6263362bcff2de76d73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cardiovascular system</topic><topic>Dose-Response Relationship, Drug</topic><topic>Electrochemistry</topic><topic>Free Radical Scavengers - pharmacology</topic><topic>In Vitro Techniques</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Nitric Oxide - pharmacology</topic><topic>Nitric Oxide Donors - pharmacology</topic><topic>Nitroprusside - pharmacology</topic><topic>Oxidative Stress</topic><topic>Oxyhemoglobins - pharmacology</topic><topic>Penicillamine - analogs & derivatives</topic><topic>Penicillamine - pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>piglet</topic><topic>pulmonary artery</topic><topic>Pulmonary Artery - drug effects</topic><topic>Pulmonary Artery - physiology</topic><topic>SNAP</topic><topic>Sodium nitroprusside</topic><topic>superoxide</topic><topic>Superoxide Dismutase - pharmacology</topic><topic>Superoxides - metabolism</topic><topic>Swine</topic><topic>Swine, Miniature</topic><topic>Vasodilation - drug effects</topic><topic>Vasodilator agents. Cerebral vasodilators</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>López‐López, José Gustavo</creatorcontrib><creatorcontrib>Pérez‐Vizcaíno, Francisco</creatorcontrib><creatorcontrib>Cogolludo, Angel L</creatorcontrib><creatorcontrib>Ibarra, Manuel</creatorcontrib><creatorcontrib>Zaragozá‐Arnáez, Francisco</creatorcontrib><creatorcontrib>Tamargo, Juan</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 Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</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>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</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>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>López‐López, José Gustavo</au><au>Pérez‐Vizcaíno, Francisco</au><au>Cogolludo, Angel L</au><au>Ibarra, Manuel</au><au>Zaragozá‐Arnáez, Francisco</au><au>Tamargo, Juan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nitric oxide‐ and nitric oxide donors‐induced relaxation and its modulation by oxidative stress in piglet pulmonary arteries</atitle><jtitle>British journal of pharmacology</jtitle><addtitle>Br J Pharmacol</addtitle><date>2001-07</date><risdate>2001</risdate><volume>133</volume><issue>5</issue><spage>615</spage><epage>624</epage><pages>615-624</pages><issn>0007-1188</issn><eissn>1476-5381</eissn><coden>BJPCBM</coden><abstract>Inhaled nitric oxide (iNO) is widely used in the treatment of pulmonary hypertension while inhaled NO donors have been suggested as an alternative therapy. The differential susceptibility to inactivation by oxidative stress and oxyhaemoglobin of NO and two NO donors, sodium nitroprusside (SNP) and S‐nitroso‐N‐acetyl‐penicillamine (SNAP) were analysed in isolated endothelium‐denuded pulmonary arteries from 2‐week‐old piglets stimulated with U46619.
NO, SNAP and SNP relaxed the arteries (pIC30=7.73±0.12, 7.26±0.17 and 6.43±0.13, respectively) but NO was not detected electrochemically in the bath after the addition of SNP and only at concentrations at which SNAP produced more than 50% relaxation.
The sGC inhibitor ODQ (10−6 M) or the sarcoplasmic Ca2+‐ATPase thapsigargin (2×10−6 M) markedly inhibited the relaxation induced by NO, SNAP and SNP.
Addition of oxyhaemoglobin (3×10−7 M) or diethyldithiocarbamate (1 mM) markedly inhibited NO‐ (pIC30=6.88±0.07 and 6.92±0.18, respectively), weakly inhibited SNAP‐ and had no effect on SNP‐induced relaxation. Xanthine oxidase (5 mu ml−1) plus hypoxanthine (10−4 M) markedly inhibited NO‐ (pIC30=6.96±0.12) but not SNAP‐ or SNP‐induced relaxation.
Superoxide dismutase (SOD), MnCl2, diphenileneiodonium and exposing the luminal surface of the rings outwards (inversion) potentiated the relaxant responses of NO (pIC30=8.52±0.16, 8.23±0.11, 8.01±0.11 and 8.20±0.10, respectively). However, SOD did not modify the NO detected by the electrode and had no effect on SNAP‐ or SNP‐induced relaxation.
Therefore, the kinetics and local distribution of NO release of NO donors influence the susceptibility to the scavenging effects of oxyhaemoglobin and superoxide.
British Journal of Pharmacology (2001) 133, 615–624; doi:10.1038/sj.bjp.0704103</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>11429384</pmid><doi>10.1038/sj.bjp.0704103</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Biological and medical sciences Cardiovascular system Dose-Response Relationship, Drug Electrochemistry Free Radical Scavengers - pharmacology In Vitro Techniques Male Medical sciences Nitric Oxide - pharmacology Nitric Oxide Donors - pharmacology Nitroprusside - pharmacology Oxidative Stress Oxyhemoglobins - pharmacology Penicillamine - analogs & derivatives Penicillamine - pharmacology Pharmacology. Drug treatments piglet pulmonary artery Pulmonary Artery - drug effects Pulmonary Artery - physiology SNAP Sodium nitroprusside superoxide Superoxide Dismutase - pharmacology Superoxides - metabolism Swine Swine, Miniature Vasodilation - drug effects Vasodilator agents. Cerebral vasodilators |
title | Nitric oxide‐ and nitric oxide donors‐induced relaxation and its modulation by oxidative stress in piglet pulmonary arteries |
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