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

Eijk, Hans M.H. van; Luiking, Yvette C.; Deutz, N.E.P.

doi:10.1016/j.jchromb.2006.08.054

Cited by 35 publications

(27 citation statements)

References 89 publications

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“…A venous blood sample was drawn for the measurement of the natural abundance of plasma amino acids in each subject, before the start of the stable isotope primedcontinuous infusion protocol. (41). Plasma enrichments of amino acid isotopes were determined by measuring the ratio of the amino acid stable isotope/ amino acid (tracer/tracee ratio) with a liquid chromatography mass spectrometry method (42).…”

Section: Methodsmentioning

confidence: 99%

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Nitric oxide and l-arginine metabolism in a devascularized porcine model of acute liver failure

Sharma

Have

Ytrebø

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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In acute liver failure (ALF), the hyperdynamic circulation is believed to be the result of overproduction of nitric oxide (NO) in the splanchnic circulation. However, it has been suggested that arginine concentrations (the substrate for NO) are believed to be decreased, limiting substrate availability for NO production. To characterize the metabolic fate of arginine in early-phase ALF, we systematically assessed its interorgan transport and metabolism and measured the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) in a porcine model of ALF. Female adult pigs (23-30 kg) were randomized to sham (N ϭ 8) or hepatic devascularization ALF (N ϭ 8) procedure for 6 h. We measured plasma arginine, citrulline, ornithine levels; arginase activity, NO, and ADMA. Whole body metabolic rates and interorgan flux measurements were calculated using stable isotope-labeled amino acids. Plasma arginine decreased Ͼ85% of the basal level at t ϭ 6 h (P Ͻ 0.001), whereas citrulline and ornithine progressively increased in ALF (P Ͻ 0.001 and P Ͻ 0.001, vs. sham respectively). No difference was found between the groups in the whole body rate of appearance of arginine or NO. However, ALF showed a significant increase in de novo arginine synthesis (P Ͻ 0.05). Interorgan data showed citrulline net intestinal production and renal consumption that was related to net renal production of arginine and ornithine. Both plasma arginase activity and plasma ADMA levels significantly increased in ALF (P Ͻ 0.001). In this model of early-phase ALF, arginine deficiency or higher ADMA levels do not limit whole body NO production. Arginine deficiency is caused by arginase-related arginine clearance in which arginine production is stimulated de novo.arginine; asymmetric dimethylarginine; arginase ACUTE LIVER FAILURE (ALF) is characterized by sudden and severe liver dysfunction with rapid progression to coagulopathy, encephalopathy, and multiorgan failure. Without liver transplantation, mortality from ALF is about 50% (4). A hallmark of ALF is the presentation of systemic hypotension and a hyperdynamic circulation (39). This is associated with increased guanylate cyclase (GC) activation by nitric oxide (NO) (33), which converts guanidine triphosphate to cyclic guanidine monophosphate and is thought to cause the vasodilatation seen in ALF (34). Previously, we have reported the characteristics of the same devascularized porcine liver model of ALF, which was shown to have a hyperdynamic circulation as evidenced by a high cardiac output and low mean arterial pressure and systemic vascular resistance (50). However, in this hyperacute model of ALF, no significant changes in the metabolites of NO were observed. Indeed, the kinetics of NO in this model and whether it is involved in the initiation of the vasodilation of ALF remain unknown.L-Arginine has several important biological functions (2, 3, 5), one of which is to be the nitrogen-donating substrate for endothelial NO synthase (eNOS) to produce NO and citrulline in stoichiometric quantities (...

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Section: Methodsmentioning

confidence: 99%

“…Whole body rate of appearances of NO was determined with the flux of plasma L-arginine to L-citrulline-stable isotopes as described previously (41). Whole body rate of appearance of de novo arginine was determined with the flux of plasma L-citrulline to L-argininestable isotopes as described previously (32).…”

Section: Methodsmentioning

confidence: 99%

Nitric oxide and l-arginine metabolism in a devascularized porcine model of acute liver failure

Sharma

Have

Ytrebø

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…An upto-date review covering the application of isotopes in the L-arginine/NO pathway, including a discussion of interferences and possible limitations of the method, was recently provided by van Eijk et al (19 ). A major advantage of the stable isotope method is that it allows to distinguish NO-derived nitrate from nitrate from other (dietary) sources.…”

Section: Infusion Ofmentioning

confidence: 99%

Simultaneous Assessment of Endothelial Function, Nitric Oxide Synthase Activity, Nitric Oxide–Mediated Signaling, and Oxidative Stress in Individuals with and without Hypercholesterolemia

et al. 2008

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BACKGROUND:Endothelial function is impaired in hypercholesterolemia and atherosclerosis. Based on mostly indirect evidence, this impairment is attributed to reduced synthesis or impaired biological activity of endothelium-derived nitric oxide (NO). It was the aim of this study to directly estimate and compare wholebody NO production in normo-and hypercholesterolemia by applying a nonradioactive stable isotope dilution technique in vivo.

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“…at a dose of >30 mg kg −1 , with complete recovery within 5 min post injection 192 . These reports, taken together with the toxic effects of DAM (45), suggest that the oxime functions of compounds that can cross the blood-brain barrier have a depressive activity in the CNS.…”

Section: Physiological Propertiesmentioning

confidence: 99%

“…At near-lethal doses, the most common toxic signs are vomiting, salivation, loss of reflexes and convulsions. Aliphatic noncharged oxime reactivators, such as DAM (45), produce mainly CNS depression, in contrast to the charged pyridinium oximes, high doses of which primarily affect cardiac muscle 182 .…”

Section: Physiological Propertiesmentioning

confidence: 99%

Hydroxylamines and Oximes: Biological Properties and Potential Uses as Therapeutic Agents

Ashani¹,

Silman²

2010

Patai's Chemistry of Functional Groups

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

Cited by 35 publications

References 89 publications

Nitric oxide and l-arginine metabolism in a devascularized porcine model of acute liver failure

Nitric oxide and l-arginine metabolism in a devascularized porcine model of acute liver failure

Simultaneous Assessment of Endothelial Function, Nitric Oxide Synthase Activity, Nitric Oxide–Mediated Signaling, and Oxidative Stress in Individuals with and without Hypercholesterolemia

Hydroxylamines and Oximes: Biological Properties and Potential Uses as Therapeutic Agents

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