Effect of growth hormone therapy on nitric oxide formation in cystic fibrosis patients.

Airway nitric oxide production is decreased in cystic fibrosis. As growth hormone therapy has been shown to increase nitric oxide production in growth hormone-deficient patients, it may also affect nitric oxide production in patients with cystic fibrosis. The objective of the present study was to investigate the effect of growth hormone therapy on systemic and airway nitric oxide formation in patients with cystic fibrosis. Nitric oxide metabolites in serum and urine, amino acid concentrations in serum and sputum, as well as exhaled nitric oxide, were measured in children with cystic fibrosis before, during and after 1 yr of treatment with human growth hormone. Nitric oxide metabolite concentrations increased significantly in serum and urine during the treatment period. Serum amino acid concentrations (including l-arginine, the substrate for nitric oxide synthases) also increased during treatment. The systemic bioavailability of l-arginine for nitric oxide synthases, expressed as ratio of l-arginine/l-ornithine+lysine, remained unchanged. In contrast, l-arginine concentrations in sputum decreased significantly during growth hormone treatment, as did exhaled nitric oxide levels. Treatment with growth hormone in children with cystic fibrosis decreases exhaled nitric oxide by reducing the concentration of l-arginine in the airways.

Effects of fetal exposure to high-fat diet or maternal hyperglycemia on L-arginine and nitric oxide metabolism in lung.

BACKGROUND/OBJECTIVES: Alterations in the L-arginine/nitric oxide (NO) metabolism contribute to diseases such as obesity, metabolic syndrome and airway dysfunction. The impact of early-life exposures on the L-arginine/NO metabolism in lung later in life is not well understood. The objective of this work was to study the effects of intrauterine exposures to maternal hyperglycemia and high-fat diet (HFD) on pulmonary L-arginine/NO metabolism in mice. METHODS: We used two murine models of intrauterine exposures to maternal (a) hyperglycemia and (b) HFD to study the effects of these exposures on the L-arginine/NO metabolism in lung in normal chow-fed offspring. RESULTS: Both intrauterine exposures resulted in NO deficiency in the lung of the offspring at 6 weeks of age. However, each of the exposures leading to different metabolic phenotypes caused a distinct alteration in the L-arginine/NO metabolism. Maternal hyperglycemia leading to impaired glucose tolerance but no obesity in the offspring resulted in increased levels of asymmetric dimethylarginine and impairment of NO synthases. Although maternal HFD led to obesity without impairment in glucose tolerance in the offspring, it resulted in increased expression and activity of arginase in the lung of the normal chow-fed offspring. CONCLUSIONS: These data suggest that maternal hyperglycemia and HFD can cause alterations in the pulmonary L-arginine/NO metabolism in offspring.

Maternal perinatal diet induces developmental programming of bone architecture.

Maternal high-fat (HF) diet can alter offspring metabolism via perinatal developmental programming. This study tests the hypothesis that maternal HF diet also induces perinatal programming of offspring bone mass and strength. We compared skeletal acquisition in pups from C57Bl/6J mice fed HF or normal diet from preconception through lactation. Three-week-old male and female pups from HF (HF-N) and normal mothers (N-N) were weaned onto normal diet. Outcomes at 14 and 26 weeks of age included body mass, body composition, whole-body bone mineral content (WBBMC) via peripheral dual-energy X-ray absorptiometry, femoral cortical and trabecular architecture via microcomputed tomography, and glucose tolerance. Female HF-N had normal body mass and glucose tolerance, with lower body fat (%) but higher serum leptin at 14 weeks vs. N-N (P<0.05 for both). WBBMC was 12% lower at 14 weeks and 5% lower at 26 weeks, but trabecular bone volume fraction was 20% higher at 14 weeks in female HF-N vs. N-N (P<0.05 for all). Male HF-N had normal body mass and mildly impaired glucose tolerance, with lower body fat (%) at 14 weeks and lower serum leptin at 26 weeks vs. N-N (P<0.05 for both). Serum insulin was higher at 14 weeks and lower at 26 weeks in HF-N vs. N-N (P<0.05). Trabecular BV/TV was 34% higher and cortical bone area was 6% higher at 14 weeks vs. N-N (P<0.05 for both). These data suggest that maternal HF diet has complex effects on offspring bone, supporting the hypothesis that maternal diet alters postnatal skeletal homeostasis.

Oral L-arginine supplementation in cystic fibrosis patients: a placebo-controlled study.

Exhaled nitric oxide (eNO) is decreased in cystic fibrosis (CF). The effect of oral L-arginine, the precursor of enzymatic nitric oxide (NO) formation, on airway NO in patients with CF was studied. In a pilot study, oral L-arginine was given in a single dose of 200 mg x kg(-1) body weight to eight healthy controls and eight CF patients. Subsequently, the same L-arginine dose was given to 10 patients with CF (five females) t.i.d. for 6 weeks in a randomised double-blind placebo-controlled crossover study. A single dose of oral L-arginine resulted in a 5.5-fold increase of L-arginine in plasma and a 1.3-fold increase of L-arginine in sputum after 2 h. Maximum eNO, within 3 h of L-arginine intake, increased significantly in both CF patients (5.4+/-2.1 ppb versus 8.3+/-3.5 ppb) and controls (18.0+/-8.1 ppb versus 26.4+/-12.3 ppb). Supplementation of L-arginine for 6 weeks resulted in a sustained increase in eNO compared to placebo (9.7+/-5.7 ppb versus 6.3+/-3.1 ppb). An effect of L-arginine supplementation on forced expiratory volume in one second was not observed. These data indicate that airway nitric oxide formation in cystic fibrosis patients can be augmented with oral L-arginine supplementation.