title: Regulation of the rate of synthesis of nitric oxide by Mg(2+) and hypoxia. Studies in rat heart mitochondria.
abstract: In isolated rat heart mitochondria, L-arginine is oxidized by a nitric oxide synthase (mtNOS) achieving maximal rates at 1 mM L-arginine. The NOS inhibitor N(G)-nitro-L-arginine methyl ester (NAME) inhibits the increase in NO production. Extramitochondrial free magnesium inhibited NOS production by 59% at 3.2 mM. The mitochondrial free Mg(2+) concentration increased to different extents in the presence of L-arginine (29%), the NO donor (S-nitroso-N-acetylpenicillamine) (105%) or the NOS inhibitors L-NAME (48%) or N(G)-nitro-L-arginine methyl ester, N(G)-monomethyl-L-arginine (L-NMMA) (53%). Under hypoxic conditions, mtNOS activity was inhibited by Mg(2+) by up to 50% after 30 min of incubation. Reoxygenation restored the activity of the mtNOS to pre-hypoxia levels. The results suggest that in heart mitochondria there is an interaction between Mg(2+) levels and mtNOS activity which in turn is modified by hypoxia and reoxygenation.
authors.affiliation: Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Michoacan 58030, México.
authors.forename: S
authors.initials: S
authors.lastname: Manzo-Avalos
authors.forename: V
authors.initials: V
authors.lastname: Pérez-Vázquez
authors.forename: J
authors.initials: J
authors.lastname: Ramírez
authors.forename: L
authors.initials: L
authors.lastname: Aguilera-Aguirre
authors.forename: J C
authors.initials: JC
authors.lastname: González-Hernández
authors.forename: M
authors.initials: M
authors.lastname: Clemente-Guerrero
authors.forename: R
authors.initials: R
authors.lastname: Villalobos-Molina
authors.forename: A
authors.initials: A
authors.lastname: Saavedra-Molina
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D008274:Magnesium / Q000502:physiology*; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D008274:Magnesium; D010100:Oxygen