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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

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, María Pilar
dc.date.accessioned	2011-07-08T08:06:54Z
dc.date.available	2011-07-08T08:06:54Z
dc.date.issued	2005
dc.identifier.citation	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.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.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	journal article	es_ES
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.identifier.idgrec	028686	en
dc.type.hasVersion	VoR	es_ES
dc.identifier.url	http://circres.ahajournals.org/cgi/reprint/97/10/1063	en