title: Hypocholesterolemic properties of nitric oxide. In vivo and in vitro studies using nitric oxide donors.
abstract: Previous results suggested that changes in the activity of nitric oxide (NO) can influence metabolism of apo B-containing lipoproteins. Therefore, we studied effects of exogenous NO donors and physiological NO precursors on metabolism of these lipoproteins. In rabbits, addition of 0.03% sodium nitroprusside (NaNP) to a semipurified, cholesterol-free, casein diet counteracted the elevation of LDL cholesterol induced by this diet but did not alter liver lipids after 4 weeks of feeding. In HepG2 cells, addition of nontoxic concentrations of another NO donor, S-nitroso-N-acetylpenicillamine (SNAP) to culture medium caused a dose-dependent reduction of medium apo B after 24 h. At the concentration 0.5 mM, SNAP significantly decreased medium apo B by 50% without altering total synthesis and secretion of proteins and without altering rates of cellular sterol synthesis. In cells incubated with L-arginine, reduction of medium apo B was not associated with increased NO production whereas in those exposed to N-OH-Arg medium apo B levels were not altered. We concluded that synthetic NO donors can reduce hypercholesterolemia by affecting apo B metabolism directly in the liver, via the sterol-independent mechanism.
authors.affiliation: Department of Biochemistry, Centre for Human Nutrition, University of Western Ontario, London, Ontario, Canada. kurowska@julian.uwo.ca
authors.forename: E M
authors.initials: EM
authors.lastname: Kurowska
authors.forename: K K
authors.initials: KK
authors.lastname: Carroll
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001055:Apolipoproteins B / Q000032:analysis; D006801:Humans; D008074:Lipoproteins / Q000032:analysis; D008099:Liver / Q000737:chemistry; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011817:Rabbits; D026423:S-Nitroso-N-Acetylpenicillamine; D014407:Tumor Cells, Cultured
chemical_list: D000924:Anticholesteremic Agents; D001055:Apolipoproteins B; D008074:Lipoproteins; D009599:Nitroprusside; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D010396:Penicillamine