Regulation of the rate of synthesis of nitric oxide by Mg(2+) and hypoxia. Studies in rat heart mitochondria

• Published in: Amino acids Vol. 22; no. 4; pp. 381 - 389
• Main Authors: Manzo-Avalos, S, Pérez-Vázquez, V, Ramírez, J, Aguilera-Aguirre, L, González-Hernández, J C, Clemente-Guerrero, M, Villalobos-Molina, R, Saavedra-Molina, A
• Format: Journal Article
• Language: English
• Published: Austria 01-06-2002
• Subjects: Animals; Cell Hypoxia; Magnesium - physiology; Male; Mitochondria, Heart - metabolism; Nitric Oxide - biosynthesis; Nitric Oxide Synthase - metabolism; Oxygen - metabolism; Rats; Rats, Wistar
• ISSN: 0939-4451
• DOI: 10.1007/s007260200022

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.