Bioactivation of nitroglycerin and vasomotor response to nitric oxide are impaired in cirrhotic rat livers
Nitroglycerin (NTG), a nitric oxide (NO) donor, has been shown to reduce portal pressure in cirrhotic patients. Using the in situ perfusion of normal and cirrhotic rat livers, we compared the vascular relaxation induced by either NTG or the spontaneous nitric oxide donor S-nitroso- N-acetylpenicilla...
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| Veröffentlicht in: | Hepatology (Baltimore, Md.) Md.), 2002-08, Vol.36 (2), p.381-385 |
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| creator | Dudenhoefer, Amy A. Loureiro-Silva, Maurı́ cio R. Cadelina, Gregory W. Gupta, Tarun Groszmann, Roberto J. |
| description | Nitroglycerin (NTG), a nitric oxide (NO) donor, has been shown to reduce portal pressure in cirrhotic patients. Using the
in situ perfusion of normal and cirrhotic rat livers, we compared the vascular relaxation induced by either NTG or the spontaneous nitric oxide donor
S-nitroso-
N-acetylpenicillamine (SNAP). Normal and cirrhotic livers were perfused (40 mL/min, 37°C) with Krebs' solution in a recirculating system. After preconstriction with methoxamine (10
−4 mol/L), a dose-response study was performed using 6 cumulative doses of NTG or SNAP (10
−7 to 3 × 10
−5 mol/L). NO
x (NO
2
− + NO[overthree]) production in the perfusate was measured by chemiluminescence. Cirrhotic livers exhibited lower vasorelaxant responses, compared with normal livers, to both NTG (
P < .0001) and SNAP (
P = .0020). In normal livers, NTG and SNAP induced similar vasorelaxant responses (
P = .44). In cirrhotic livers, NTG induced less vasorelaxation than SNAP (
P < .0001). In the presence of NTG (
P = .0045), but not SNAP (
P = .99), NO
x production in experiments with cirrhotic livers was lower than in experiments with normal livers. In conclusion, in cirrhotic rat livers, the vasorelaxant response to NTG is impaired owing to both a decreased metabolism of this NO donor and an inability of the hepatic vasculature to respond to NO. (H
EPATOLOGY 2002;36:381-385.) |
| doi_str_mv | 10.1053/jhep.2002.34739 |
| format | Article |
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in situ perfusion of normal and cirrhotic rat livers, we compared the vascular relaxation induced by either NTG or the spontaneous nitric oxide donor
S-nitroso-
N-acetylpenicillamine (SNAP). Normal and cirrhotic livers were perfused (40 mL/min, 37°C) with Krebs' solution in a recirculating system. After preconstriction with methoxamine (10
−4 mol/L), a dose-response study was performed using 6 cumulative doses of NTG or SNAP (10
−7 to 3 × 10
−5 mol/L). NO
x (NO
2
− + NO[overthree]) production in the perfusate was measured by chemiluminescence. Cirrhotic livers exhibited lower vasorelaxant responses, compared with normal livers, to both NTG (
P < .0001) and SNAP (
P = .0020). In normal livers, NTG and SNAP induced similar vasorelaxant responses (
P = .44). In cirrhotic livers, NTG induced less vasorelaxation than SNAP (
P < .0001). In the presence of NTG (
P = .0045), but not SNAP (
P = .99), NO
x production in experiments with cirrhotic livers was lower than in experiments with normal livers. In conclusion, in cirrhotic rat livers, the vasorelaxant response to NTG is impaired owing to both a decreased metabolism of this NO donor and an inability of the hepatic vasculature to respond to NO. (H
EPATOLOGY 2002;36:381-385.)</description><identifier>ISSN: 0270-9139</identifier><identifier>EISSN: 1527-3350</identifier><identifier>DOI: 10.1053/jhep.2002.34739</identifier><identifier>PMID: 12143046</identifier><identifier>CODEN: HPTLD9</identifier><language>eng</language><publisher>Philadelphia, PA: Elsevier Inc</publisher><subject>Animals ; Biological and medical sciences ; Digestive system ; Liver - metabolism ; Liver - pathology ; Liver Cirrhosis, Experimental - drug therapy ; Liver Cirrhosis, Experimental - metabolism ; Liver Cirrhosis, Experimental - pathology ; Male ; Medical sciences ; Nitrates - metabolism ; Nitric Oxide - metabolism ; Nitric Oxide Donors - pharmacology ; Nitrites - metabolism ; Nitroglycerin - metabolism ; Nitroglycerin - pharmacology ; Organ Size ; Pharmacology. Drug treatments ; Rats ; Rats, Sprague-Dawley ; S-Nitroso-N-Acetylpenicillamine - pharmacology ; Vasodilator Agents - metabolism ; Vasodilator Agents - pharmacology</subject><ispartof>Hepatology (Baltimore, Md.), 2002-08, Vol.36 (2), p.381-385</ispartof><rights>2002 The American Association for the Study of Liver Diseases</rights><rights>Copyright © 2002 American Association for the Study of Liver Diseases</rights><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5305-c9cb4fda7ce4a103bb1804e9d05755de78f225ee3073ce8257994b9b56dfe5da3</citedby><cites>FETCH-LOGICAL-c5305-c9cb4fda7ce4a103bb1804e9d05755de78f225ee3073ce8257994b9b56dfe5da3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1053%2Fjhep.2002.34739$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1053%2Fjhep.2002.34739$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13831689$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12143046$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dudenhoefer, Amy A.</creatorcontrib><creatorcontrib>Loureiro-Silva, Maurı&#x0301;cio R.</creatorcontrib><creatorcontrib>Cadelina, Gregory W.</creatorcontrib><creatorcontrib>Gupta, Tarun</creatorcontrib><creatorcontrib>Groszmann, Roberto J.</creatorcontrib><title>Bioactivation of nitroglycerin and vasomotor response to nitric oxide are impaired in cirrhotic rat livers</title><title>Hepatology (Baltimore, Md.)</title><addtitle>Hepatology</addtitle><description>Nitroglycerin (NTG), a nitric oxide (NO) donor, has been shown to reduce portal pressure in cirrhotic patients. Using the
in situ perfusion of normal and cirrhotic rat livers, we compared the vascular relaxation induced by either NTG or the spontaneous nitric oxide donor
S-nitroso-
N-acetylpenicillamine (SNAP). Normal and cirrhotic livers were perfused (40 mL/min, 37°C) with Krebs' solution in a recirculating system. After preconstriction with methoxamine (10
−4 mol/L), a dose-response study was performed using 6 cumulative doses of NTG or SNAP (10
−7 to 3 × 10
−5 mol/L). NO
x (NO
2
− + NO[overthree]) production in the perfusate was measured by chemiluminescence. Cirrhotic livers exhibited lower vasorelaxant responses, compared with normal livers, to both NTG (
P < .0001) and SNAP (
P = .0020). In normal livers, NTG and SNAP induced similar vasorelaxant responses (
P = .44). In cirrhotic livers, NTG induced less vasorelaxation than SNAP (
P < .0001). In the presence of NTG (
P = .0045), but not SNAP (
P = .99), NO
x production in experiments with cirrhotic livers was lower than in experiments with normal livers. In conclusion, in cirrhotic rat livers, the vasorelaxant response to NTG is impaired owing to both a decreased metabolism of this NO donor and an inability of the hepatic vasculature to respond to NO. (H
EPATOLOGY 2002;36:381-385.)</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Digestive system</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>Liver Cirrhosis, Experimental - drug therapy</subject><subject>Liver Cirrhosis, Experimental - metabolism</subject><subject>Liver Cirrhosis, Experimental - pathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Nitrates - metabolism</subject><subject>Nitric Oxide - metabolism</subject><subject>Nitric Oxide Donors - pharmacology</subject><subject>Nitrites - metabolism</subject><subject>Nitroglycerin - metabolism</subject><subject>Nitroglycerin - pharmacology</subject><subject>Organ Size</subject><subject>Pharmacology. Drug treatments</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>S-Nitroso-N-Acetylpenicillamine - pharmacology</subject><subject>Vasodilator Agents - metabolism</subject><subject>Vasodilator Agents - pharmacology</subject><issn>0270-9139</issn><issn>1527-3350</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkD1v2zAQhomiReOknbsVXNpNDj9EUxzbIG0KBEiHZCYo8tScIYkqSTv1v48cG_AUdLrhnvc93EPIJ86WnCl5uX6EaSkYE0tZa2nekAVXQldSKvaWLJjQrDJcmjNynvOaMWZq0bwnZ1zwWrJ6tSDr7xidL7h1BeNIY0dHLCn-6XceEo7UjYFuXY5DLDHRBHmKYwZa4guHnsZ_GIC6BBSHyWGCQOeYx5QeY5n3yRXa4xZS_kDeda7P8PE4L8jDj-v7q5vq9u7nr6tvt5VXkqnKG9_WXXDaQ-04k23LG1aDCUxppQLophNCAUimpYdGKG1M3ZpWrUIHKjh5Qb4eeqcU_24gFztg9tD3boS4yVZzo7gUcgYvD6BPMecEnZ0SDi7tLGd2r9fu9dq9Xvuid058PlZv2gHCiT_6nIEvR8Bl7_ouudFjPnGykXzV7IvMgXvCHnb_u2tvrn-rWcWKCa5OWZglbhGSzR5h9BBm-77YEPHVB54B08ap6A</recordid><startdate>200208</startdate><enddate>200208</enddate><creator>Dudenhoefer, Amy A.</creator><creator>Loureiro-Silva, Maurı&#x0301;cio R.</creator><creator>Cadelina, Gregory W.</creator><creator>Gupta, Tarun</creator><creator>Groszmann, Roberto J.</creator><general>Elsevier Inc</general><general>W.B. Saunders</general><general>Wiley</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>7X8</scope></search><sort><creationdate>200208</creationdate><title>Bioactivation of nitroglycerin and vasomotor response to nitric oxide are impaired in cirrhotic rat livers</title><author>Dudenhoefer, Amy A. ; Loureiro-Silva, Maurı&#x0301;cio R. ; Cadelina, Gregory W. ; Gupta, Tarun ; Groszmann, Roberto J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5305-c9cb4fda7ce4a103bb1804e9d05755de78f225ee3073ce8257994b9b56dfe5da3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Digestive system</topic><topic>Liver - metabolism</topic><topic>Liver - pathology</topic><topic>Liver Cirrhosis, Experimental - drug therapy</topic><topic>Liver Cirrhosis, Experimental - metabolism</topic><topic>Liver Cirrhosis, Experimental - pathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Nitrates - metabolism</topic><topic>Nitric Oxide - metabolism</topic><topic>Nitric Oxide Donors - pharmacology</topic><topic>Nitrites - metabolism</topic><topic>Nitroglycerin - metabolism</topic><topic>Nitroglycerin - pharmacology</topic><topic>Organ Size</topic><topic>Pharmacology. Drug treatments</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>S-Nitroso-N-Acetylpenicillamine - pharmacology</topic><topic>Vasodilator Agents - metabolism</topic><topic>Vasodilator Agents - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dudenhoefer, Amy A.</creatorcontrib><creatorcontrib>Loureiro-Silva, Maurı&#x0301;cio R.</creatorcontrib><creatorcontrib>Cadelina, Gregory W.</creatorcontrib><creatorcontrib>Gupta, Tarun</creatorcontrib><creatorcontrib>Groszmann, Roberto J.</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>MEDLINE - Academic</collection><jtitle>Hepatology (Baltimore, Md.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dudenhoefer, Amy A.</au><au>Loureiro-Silva, Maurı&#x0301;cio R.</au><au>Cadelina, Gregory W.</au><au>Gupta, Tarun</au><au>Groszmann, Roberto J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bioactivation of nitroglycerin and vasomotor response to nitric oxide are impaired in cirrhotic rat livers</atitle><jtitle>Hepatology (Baltimore, Md.)</jtitle><addtitle>Hepatology</addtitle><date>2002-08</date><risdate>2002</risdate><volume>36</volume><issue>2</issue><spage>381</spage><epage>385</epage><pages>381-385</pages><issn>0270-9139</issn><eissn>1527-3350</eissn><coden>HPTLD9</coden><abstract>Nitroglycerin (NTG), a nitric oxide (NO) donor, has been shown to reduce portal pressure in cirrhotic patients. Using the
in situ perfusion of normal and cirrhotic rat livers, we compared the vascular relaxation induced by either NTG or the spontaneous nitric oxide donor
S-nitroso-
N-acetylpenicillamine (SNAP). Normal and cirrhotic livers were perfused (40 mL/min, 37°C) with Krebs' solution in a recirculating system. After preconstriction with methoxamine (10
−4 mol/L), a dose-response study was performed using 6 cumulative doses of NTG or SNAP (10
−7 to 3 × 10
−5 mol/L). NO
x (NO
2
− + NO[overthree]) production in the perfusate was measured by chemiluminescence. Cirrhotic livers exhibited lower vasorelaxant responses, compared with normal livers, to both NTG (
P < .0001) and SNAP (
P = .0020). In normal livers, NTG and SNAP induced similar vasorelaxant responses (
P = .44). In cirrhotic livers, NTG induced less vasorelaxation than SNAP (
P < .0001). In the presence of NTG (
P = .0045), but not SNAP (
P = .99), NO
x production in experiments with cirrhotic livers was lower than in experiments with normal livers. In conclusion, in cirrhotic rat livers, the vasorelaxant response to NTG is impaired owing to both a decreased metabolism of this NO donor and an inability of the hepatic vasculature to respond to NO. (H
EPATOLOGY 2002;36:381-385.)</abstract><cop>Philadelphia, PA</cop><pub>Elsevier Inc</pub><pmid>12143046</pmid><doi>10.1053/jhep.2002.34739</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Hepatology (Baltimore, Md.), 2002-08, Vol.36 (2), p.381-385 |
| issn | 0270-9139 1527-3350 |
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| source | MEDLINE; Access via Wiley Online Library; EZB-FREE-00999 freely available EZB journals |
| subjects | Animals Biological and medical sciences Digestive system Liver - metabolism Liver - pathology Liver Cirrhosis, Experimental - drug therapy Liver Cirrhosis, Experimental - metabolism Liver Cirrhosis, Experimental - pathology Male Medical sciences Nitrates - metabolism Nitric Oxide - metabolism Nitric Oxide Donors - pharmacology Nitrites - metabolism Nitroglycerin - metabolism Nitroglycerin - pharmacology Organ Size Pharmacology. Drug treatments Rats Rats, Sprague-Dawley S-Nitroso-N-Acetylpenicillamine - pharmacology Vasodilator Agents - metabolism Vasodilator Agents - pharmacology |
| title | Bioactivation of nitroglycerin and vasomotor response to nitric oxide are impaired in cirrhotic rat livers |
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