A technique to estimate the rate of whole body nitric oxide formation in conscious mice

Wickman, Anna; Klintland, Natalia; Gan, Li‐Ming; Sakinis, Augustinas; Söderling, Ann-Sofie; Bergström, Göran; Caidahl, Kenneth

doi:10.1016/j.niox.2003.09.001

Cited by 15 publications

(12 citation statements)

References 19 publications

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“…The amount of nitrate (0.1 mmol·kg −1 ·d −1 ) was chosen in an attempt to replenish what is normally produced by eNOS. Total body production of NO in mice has been estimated to 0.2 mmol·kg −1 ·d −1 using a GC/MS technique (19) and under normal conditions up to 70% of this is derived from eNOS (20). In dietary terms, the chosen nitrate dose corresponds to a daily intake of 100 to 300 g of a nitrate-rich vegetable, such as spinach, lettuce, or beetroot in humans (10).…”

Section: Resultsmentioning

confidence: 99%

Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice

Carlström

Larsen

Nyström

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

331

246

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The metabolic syndrome is a clustering of risk factors of metabolic origin that increase the risk for cardiovascular disease and type 2 diabetes. A proposed central event in metabolic syndrome is a decrease in the amount of bioavailable nitric oxide (NO) from endothelial NO synthase (eNOS). Recently, an alternative pathway for NO formation in mammals was described where inorganic nitrate, a supposedly inert NO oxidation product and unwanted dietary constituent, is serially reduced to nitrite and then NO and other bioactive nitrogen oxides. Here we show that several features of metabolic syndrome that develop in eNOS-deficient mice can be reversed by dietary supplementation with sodium nitrate, in amounts similar to those derived from eNOS under normal conditions. In humans, this dose corresponds to a rich intake of vegetables, the dominant dietary nitrate source. Nitrate administration increased tissue and plasma levels of bioactive nitrogen oxides. Moreover, chronic nitrate treatment reduced visceral fat accumulation and circulating levels of triglycerides and reversed the prediabetic phenotype in these animals. In rats, chronic nitrate treatment reduced blood pressure and this effect was also present during NOS inhibition. Our results show that dietary nitrate fuels a nitratenitrite-NO pathway that can partly compensate for disturbances in endogenous NO generation from eNOS. These findings may have implications for novel nutrition-based preventive and therapeutic strategies against cardiovascular disease and type 2 diabetes.glucose | insulin | s-nitrosothiol | obesity | bacteria

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Section: Resultsmentioning

confidence: 99%

Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice

Carlström

Larsen

Nyström

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

331

246

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“…One approach makes use of the inhalation of a stable-isotope labeled oxygen ( 18 O 2 ), which is subsequently converted to N 18 O and in addition to N 18 O 3 − [26]. Alternatively, the infusion of labeled nitrate [27] or labeled l-arginine [28][29][30][31][32][33][34] is applied with subsequent measurement of labeled nitrate in blood or urine.…”

Section: Stable-isotope Approach In Nitrate/nitrite Analysismentioning

confidence: 99%

Methods using stable isotopes to measure nitric oxide (NO) synthesis in the l-arginine/NO pathway in health and disease

Eijk

Luiking

Deutz

2007

Journal of Chromatography B

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“…A young bGH mouse was excluded due to possible infection. The procedure for evaluation of NO formation rate in mice has been described in detail previously [17]. In brief, mice were pairwise exposed to a gas mixture containing 18 O 2 (> 97 % isotope purity; Larodan Fine Chemicals), 16 O 2 and air for 2 h in a closed gas-tight cage system.…”

Section: No Formation Ratementioning

confidence: 99%

“…During isoflurane anaesthesia, a 200 µl sample of whole blood was collected from the orbital vein directly before (< 5 min) and after gas exposure. Plasma collected in EDTA was frozen for later analysis of newly formed 18 O 2 -labelled nitrate by GC/MS [17]. Calculations of total-body NO formation rate (µmol · h −1 · kg −1 of body weight) were performed as described previously [17].…”

Section: No Formation Ratementioning

confidence: 99%

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Endothelial dysfunction in growth hormone transgenic mice

et al. 2006

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Acromegaly [overproduction of GH (growth hormone)] is associated with cardiovascular disease. Transgenic mice overexpressing bGH (bovine GH) develop hypertension and hypercholesterolaemia and could be a model for cardiovascular disease in acromegaly. The aims of the present study were to investigate the effects of excess GH on vascular function and to test whether oxidative stress affects endothelial function in bGH transgenic mice. We studied the ACh (acetylcholine)-induced relaxation response in aortic and carotid rings of young (9-11 weeks) and aged (22-24 weeks) female bGH transgenic mice and littermate control mice, without and with the addition of a free radical scavenger {MnTBAP [Mn(III)tetrakis(4-benzoic acid)porphyrin chloride]}. We also measured mRNA levels of eNOS (endothelial nitric oxide synthase) and EC-SOD (extracellular superoxide dismutase). Intracellular superoxide anion production in the vascular wall was estimated using a dihydroethidium probe. Carotid arteries from bGH transgenic mice had an impaired ACh-induced relaxation response (young, 46 +/- 7% compared with 69 +/- 8%; aged, 52 +/- 5% compared with 80 +/- 3%; P < 0.05), whereas endothelial function in aorta was intact in young but impaired in aged bGH transgenic mice. Endothelial dysfunction was corrected by addition of MnTBAP in carotid arteries from young mice and in aortas from aged mice; however, MnTBAP did not correct endothelial dysfunction in carotid arteries from aged bGH transgenic mice. There was no difference in intracellular superoxide anion production between bGH transgenic mice and control mice, whereas mRNA expression of EC-SOD and eNOS was increased in aortas from young bGH transgenic mice compared with control mice (P < 0.05). We interpret these data to suggest that bGH overexpression is associated with a time- and vessel-specific deterioration in endothelial function, initially caused by increased oxidative stress and later by other alterations in vascular function.

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A technique to estimate the rate of whole body nitric oxide formation in conscious mice

Cited by 15 publications

References 19 publications

Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice

Dietary inorganic nitrate reverses features of metabolic syndrome in endothelial nitric oxide synthase-deficient mice

Methods using stable isotopes to measure nitric oxide (NO) synthesis in the l-arginine/NO pathway in health and disease

Endothelial dysfunction in growth hormone transgenic mice

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