Nitric oxide activity in childhood hypertension

Goonasekera, Chulananda; Shah, Vanita; Rees, Daryl D.; Dillon, M J

doi:10.1136/adc.77.1.11

Cited by 18 publications

(14 citation statements)

References 44 publications

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“…This finding agrees with other independent research groups who reported high levels of urinary nitrate excretion (index of NO synthesis) in infancy that declined with age (35)(36)(37). A similar age-related decrease was also observed in plasma (6,37) and cerebrospinal fluid nitrate concentrations (38). Furthermore, analyzing the data presented in a previous study of convalescent, treated newborns with pulmonary hypertension (5) 15 N]nitrate enrichments in the range of 0.5%-1.2% with mass spectrometry.…”

Section: Subjectssupporting

confidence: 92%

“…Accumulating evidence suggest that the NO signaling pathway is abnormal in a number of pediatric conditions including primary pulmonary hypertension (5), childhood essential hypertension (6), and cerebral malaria (7) and markedly increased in others such as septic shock (8), gastroenteritis (9,10), bronchial asthma (11), type 1 diabetes mellitus (12), and autoimmune and inflammatory diseases (13). Accurate and reliable determination of NO synthesis in vivo is essential to understand the pathophysiologic and therapeutic roles of this biologic pathway.…”

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confidence: 99%

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A Noninvasive, Sensitive, Specific, and Reliable Approach to Assess Whole-Body Nitric Oxide Synthesis in Children

2006

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Determination of nitric oxide (NO) synthesis in vivo is essential to understand the pathophysiologic role and therapeutic implications of the L-arginine/NO pathway in pediatric diseases. The aim of this study was to establish a noninvasive, sensitive, specific, and reliable approach to determine whole-body NO synthesis in healthy children. Seventeen healthy children (eight boys/nine girls, 4 -16 y) were studied twice, and six of them on three occasions. Fasting children received a single oral dose of nonradioactive T he L-arginine/NO pathway has been an exciting research area for the past two decades. NO is endogenously synthesized from the amino acid L-arginine by NO synthase (NOS) in numerous cells, including platelets, neurons, macrophages, and endothelial cells (1). Three isoforms of human NOS have been cloned: neuronal, endothelial, and inducible (2). Both the neuronal NOS and endothelial NOS are constitutively expressed in cells and produce picomolar amounts of NO. By contrast, the inducible isoform produces high and sustained levels of NO and is usually expressed in macrophages and vascular smooth muscle cells following the exposure to cytokines and lipopolysaccharide (3). The physiologic importance of the L-arginine/NO pathway has been extensively studied in humans. It is known to play a major role in controlling vascular tone, platelet function, neurotransmission, and bronchial airway reactivity (1,4).Basic research on NO derived from in vitro and in vivo experimental models has started to have an impact on pediatrics. Accumulating evidence suggest that the NO signaling pathway is abnormal in a number of pediatric conditions including primary pulmonary hypertension (5), childhood essential hypertension (6), and cerebral malaria (7) and markedly increased in others such as septic shock (8), gastroenteritis (9,10), bronchial asthma (11), type 1 diabetes mellitus (12), and autoimmune and inflammatory diseases (13). Accurate and reliable determination of NO synthesis in vivo is essential to understand the pathophysiologic and therapeutic roles of this biologic pathway. Direct measurement of exhaled NO is a noninvasive and practical approach for assessing airway inflammation in children (14). Indeed, exhaled NO has been proposed as a tool for screening and monitoring airway inflammation and titration of anti-inflammatory therapy in asthmatic children (15). On the other hand, determination of systemic NO synthesis has been proved difficult because of NO's short plasma half-life (3-5 s) (16). This limitation has led to the development of functional and chemical markers to determine NO bioactivity. Biomarkers such as cyclic guanosine monophosphate, L-citrulline, and nitrate concentrations in plasma and urine have been used in clinical studies to assess systemic NO synthesis. However, these metabolites are not specific for the L-arginine/NO pathway (17). An approach to assess whole-body NO synthesis in critically ill children (i.e. septic shock) consists of a primed, 5-8-h constant i.

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Section: Subjectssupporting

confidence: 92%

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A Noninvasive, Sensitive, Specific, and Reliable Approach to Assess Whole-Body Nitric Oxide Synthesis in Children

2006

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“…Because NO is rapidly metabolized to nitrite and nitrate (NO x ), which are relatively slowly excreted in urine without diurnal variation, urinary excretion of NO 3 is now regarded as an indicator of endogenous NO formation. Because it has been proposed that PNO 3 concentration be used as an index of NO generation in vivo [2,8,9,10,17,18], we also used PNO 3 and UNO 3 /U cr as reliable markers of endogenous NO activity.…”

Section: Discussionmentioning

confidence: 99%

“…These stable end products in biological fluids, including urine, have been measured as an index of in-vivo NOS activity [2,8,9,10,11]. The aim of this study was to determine the age-related normal reference range of plasma and urinary NO 3 and to assess the variability of urinary NO 3 excretion and glomerular filtration rate (GFR) with age.…”

Section: Introductionmentioning

confidence: 99%

Plasma and urine nitric oxide levels in healthy Turkish children

et al. 2005

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Nitric oxide (NO) is an important messenger molecule with a wide range of actions in virtually all cell systems and organs. In kidneys it participates in glomerular and medullary hemodynamics, tubuloglomerular feed-back, renin secretion, and extracellular fluid balance. Although the role of NO in regulating renal function in adults is well-established, it has recently been suggested that NO has a more critical role in maintaining basal renal blood flow and glomerular filtration rate (GFR) in the developing kidney. NO is rapidly metabolized to the stable end products nitrite and nitrate, which are more slowly excreted into the urine. Thus these metabolites can be recommended as useful markers of endogenous NO synthase activity, despite limited data about age-related changes in in-vivo NO production. The aims of this study were to determine age-related normal reference values of serum and urinary NO metabolites and to assess the probable relationship between these metabolites and the GFR. Normal levels of NO end products in blood and urine of 296 healthy children (117 female, 179 male) between the ages of 0 and 16 were investigated, as was whether these values change with age. Serum and urinary nitrate levels did not differ according to sex. Serum nitrate levels are higher in younger children, especially in the newborn period, and decrease with age. Nitrate levels in urine are higher in younger children with a peak in infancy (1 month to 1 year) and decrease with age. It was demonstrated that this decrease in serum and urinary nitrate levels with age parallels the increase in GFR. In conclusion, urinary NO products may be an indirect marker of serum NO levels and NO might have an important regulatory function both in the maintenance of renal function and in the maturation of the developing kidneys.

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“…38 In another study of 31 hypertensive and 9 healthy, normotensive children and young adults, hypertensive children displayed significantly higher levels of VCAM-1. 54 In adults, however, hypertension is not correlated with sVCAM-1 and sICAM-1.…”

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confidence: 97%