Functional characterization of brain mitochondrial nitric oxide synthase during hypertension and aging.
Nitric oxide (NO*) plays an important role in various physiological processes. The aim of the present study was to investigate if brain mitochondrial nitric oxide synthase (mtNOS) is active and functional during hypertension. L-citrulline production, an indicator of nitric oxide synthesis, was concentration-dependent on L-arginine in all strains and all ages tested, and was inhibited by 7-Nitroindazole (7-NI). Brain mitochondria of 1 month-old (prehypertensive) spontaneously hypertensive rats (SHR) exhibited a significantly (p < 0.05) low basal L-citrulline content as compared to age-matched Wistar (W) and Wistar-Kyoto (WKY) rats. L-citrulline synthesis in SHR rats showed a significant (p < 0.01) low response to L-arginine in 3 and 7 months-old rats. Respiratory rates in states 3 and 4 increased with low L-arginine concentration in all strains and all ages. The results suggest that in rat brain mitochondria, L-citrulline synthesis is constant once age-related hypertension is installed and NO* does not regulate oxidative phosphorylation.
Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Mich. México.
E
E
Calderón-Cortés
M
M
Clemente-Guerrero
E
E
Sierra-Campos
C
C
Cortés-Rojo
F J
FJ
Gaona-Zamudio
R
R
Villalobos-Molina
A
A
Saavedra-Molina
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002956:Citrulline / Q000096:biosynthesis; D006973:Hypertension / Q000201:enzymology*; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar
D007191:Indazoles; D002956:Citrulline; D001120:Arginine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; C080122:7-nitroindazole