Discrepancies Between Nitroglycerin and NO-Releasing Drugs on Mitochondrial Oxygen Consumption, Vasoactivity, and the Release of NO
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Discrepancies Between Nitroglycerin and NO-Releasing Drugs on Mitochondrial Oxygen Consumption, Vasoactivity, and the Release of NO

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Discrepancies Between Nitroglycerin and NO-Releasing Drugs on Mitochondrial Oxygen Consumption, Vasoactivity, and the Release of NO

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dc.contributor.author Nuñez, Cristina
dc.contributor.author Víctor González, Víctor Manuel
dc.contributor.author Tur, Remedios
dc.contributor.author Alvarez Barrientos, Alberto
dc.contributor.author Moncada, Salvador
dc.contributor.author Esplugues Mota, Juan Vicente
dc.contributor.author D'Ocon Navaza, Pilar
dc.date.accessioned 2011-07-08T08:06:54Z
dc.date.available 2011-07-08T08:06:54Z
dc.date.issued 2005
dc.identifier.uri http://hdl.handle.net/10550/19523
dc.description.abstract It has been generally acknowledged that the actions of glyceryl trinitrate (GTN) are a result of its bioconversion into NO. However, recent observations have thrown this idea into doubt, with many studies demonstrating that NO is present only when there are high concentrations of GTN. We have explored this discrepancy by developing a new approach that uses confocal microscopy to directly detect NO. Intracellular levels of NO in the rat aortic vascular wall have been compared with those present after incubation with 3 different NO donors (DETA-NO, 3 morpholinosydnonimine, and S-nitroso-N-acetylpenicillamine), endothelial activation with acetylcholine, or administration of GTN. We have also evaluated the relaxant effects of these treatments on isolated rings of aorta following activation of the enzyme soluble guanylyl cyclase and their inhibitory action on mitochondrial respiration, which is an index of the interaction of NO with the enzyme of the electron transport chain cytochrome C oxidase. In the case of the various NO donors and acetylcholine, we detected a concentration-dependent relationship in the intensity of vascular relaxation and degree of NO fluorescence and an increase in the Michaelis constant (Km) for O2. GTN did not produce similar effects, and although clinically relevant concentrations of this compound caused clear, concentration-related relaxations, there was neither any increase in NO-related fluorescence nor an augmented Km for O2. The nature of these differences suggests that these concentrations of GTN do not release free NO but probably a different species that, although it interacts with soluble guanylyl cyclase in vascular smooth muscle, does not inhibit O2 consumption by vascular mitochondria. en
dc.language.iso en en
dc.relation http://circres.ahajournals.org/cgi/reprint/97/10/1063 en
dc.source NUÑEZ, Cristina ; Víctor González, Víctor Manuel ; Tur, Remedios ; Alvarez-Barrientos, Alberto ; Moncada, Salvador ; Esplugues Mota, Juan Vicente ; d'Ocon Navaza, Maria Pilar, 2005, Discrepancies Between Nitroglycerin and NO-Releasing Drugs on Mitochondrial Oxygen Consumption, Vasoactivity, and the Release of NO, Circulation Research, vol. 97, no. 10, p. 1063-1069 en
dc.subject Glyceryl trinitrate ; Nitric oxide ; Mitochondria ; Vascular relaxation ; NO donors en
dc.title Discrepancies Between Nitroglycerin and NO-Releasing Drugs on Mitochondrial Oxygen Consumption, Vasoactivity, and the Release of NO en
dc.type info:eu-repo/semantics/article en
dc.type info:eu-repo/semantics/publishedVersion en
dc.subject.unesco UNESCO::CIENCIAS MÉDICAS en
dc.subject.unesco UNESCO::CIENCIAS MÉDICAS ::Farmacodinámica en
dc.identifier.doi 10.1161/01.RES.0000190588.84680.34 en
dc.description.private Victor Gonzalez, Victor Manuel, Victor.Victor@uv.es ; Esplugues Mota, Juan Vicente, Juan.V.Esplugues@uv.es ; d'Ocon Navaza, Maria Pilar, M.Pilar.Docon@uv.es en
dc.identifier.idgrec 028686 en

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