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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1996-6-6
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pubmed:abstractText |
The aim of the present study was: 1) to determine the effects of the novel selective inhibitor of guanylyl cyclase, ODQ (1H-[1,2,4]oxadiazolo[4,3,-a]quinoxaline-1-one) on basal and agonist-stimulated cyclic GMP levels in cultured porcine aortic endothelial cells and bovine pulmonary artery strips; 2) to determine its effects on agonist-induced relaxations of bovine pulmonary artery strips; and 3) to compare pulmonary artery cyclic GMP levels with vessel relaxation. ODQ (1 nM-30 microM) inhibited cyclic GMP accumulation in endothelial cells stimulated with S-nitrosoglutathione, nitroprusside and 3-morpholine-sydnonimine at IC50 values of 40 to 100 nM. Complete suppression of cyclic GMP generation was observed at approximately 10 microM. Relaxation of pulmonary artery strips induced by S-nitrosoglutathione, nitroprusside, glycerol trinitrate, nitrite (all endothelium-independent), bradykinin and the Ca++ ionophore A23187 (endothelium-dependent) were antagonized by ODQ (1-10 microM) in a concentration-dependent way. A consistent feature of the inhibitor was that maximal relaxant effects also were reduced. Basal levels and agonist-induced increases in arterial tissue cyclic GMP were inhibited in the same concentration range. However, tissue cyclic GMP production correlated poorly with pulmonary artery relaxation in that relaxations induced by S-nitrosoglutathione were only inhibited in part (50%), whereas rises in cyclic GMP were abolished completely by ODQ (10 microM). Furthermore, at 1 microM, ODQ had no effect on relaxation induced by endothelium-dependent agonists, but prevented entirely stimulation of cyclic GMP accumulation in arterial tissue. These results suggest that ODQ inhibits nitrovasodilator-induced and endothelium-dependent relaxation through inhibition of guanylyl cyclase activation, but also point to the presence of a cyclic GMP-independent component of relaxation in bovine pulmonary artery.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1H-(1,2,4)oxadiazolo(4,3-a)quinoxali...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic GMP,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Guanylate Cyclase,
http://linkedlifedata.com/resource/pubmed/chemical/Nitroglycerin,
http://linkedlifedata.com/resource/pubmed/chemical/Nitroso Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Oxadiazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Quinoxalines,
http://linkedlifedata.com/resource/pubmed/chemical/S-Nitrosoglutathione
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0022-3565
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
48-53
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:8613957-Animals,
pubmed-meshheading:8613957-Cattle,
pubmed-meshheading:8613957-Cells, Cultured,
pubmed-meshheading:8613957-Cyclic GMP,
pubmed-meshheading:8613957-Endothelium, Vascular,
pubmed-meshheading:8613957-Enzyme Inhibitors,
pubmed-meshheading:8613957-Glutathione,
pubmed-meshheading:8613957-Guanylate Cyclase,
pubmed-meshheading:8613957-Nitroglycerin,
pubmed-meshheading:8613957-Nitroso Compounds,
pubmed-meshheading:8613957-Oxadiazoles,
pubmed-meshheading:8613957-Pulmonary Artery,
pubmed-meshheading:8613957-Quinoxalines,
pubmed-meshheading:8613957-S-Nitrosoglutathione,
pubmed-meshheading:8613957-Swine,
pubmed-meshheading:8613957-Vasodilation
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pubmed:year |
1996
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pubmed:articleTitle |
Novel guanylyl cyclase inhibitor potently inhibits cyclic GMP accumulation in endothelial cells and relaxation of bovine pulmonary artery.
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pubmed:affiliation |
Institut für Pharmakologie und Toxikologie, Universität Graz, Austria.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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