title: Inhaled nitric oxide increases urinary nitric oxide metabolites and cyclic guanosine monophosphate in premature infants: relationship to pulmonary outcome.
abstract: OBJECTIVE
  Inhaled nitric oxide (iNO) has been tested to prevent bronchopulmonary dysplasia (BPD) in premature infants, however, the role of cyclic guanosine monophosphate (cGMP) is not known. We hypothesized that levels of NO metabolites (NOx) and cGMP in urine, as a noninvasive source for biospecimen collection, would reflect the dose of iNO and relate to pulmonary outcome.
  
  
  METHODS
  Studies were performed on 125 infants who required mechanical ventilation at 7 to 14 days and received 24 days of iNO at 20-2 ppm. A control group of 19 infants did not receive iNO.
  
  
  RESULTS
  In NO-treated infants there was a dose-dependent increase of both NOx and cGMP per creatinine (maximal 3.1- and 2-fold, respectively, at 10-20 ppm iNO) compared with off iNO. NOx and cGMP concentrations at both 2 ppm and off iNO were inversely related to severity of lung disease during the 1st month, and the NOx levels were lower in infants who died or developed BPD at term. NOx was higher in Caucasian compared with other infants at all iNO doses.
  
  
  CONCLUSIONS
  Urinary NOx and cGMP are biomarkers of endogenous NO production and lung uptake of iNO, and some levels reflect the severity of lung disease. These results support a role of the NO-cGMP pathway in lung development.
authors: Department of Pediatrics, University of California, San Francisco, California.
authors: Philip L
authors: PL
authors: Ballard
authors: Department of Pediatrics, University of California, San Francisco, California.
authors: Roberta L
authors: RL
authors: Keller
authors: Department of Epidemiology and Biostatistics, University of California, San Francisco, California.
authors: Dennis M
authors: DM
authors: Black
authors: Division of Neonatology, Children's Hospital and Research Center Oakland, Oakland, California.
authors: David J
authors: DJ
authors: Durand
authors: Division of Neonatology, Children's Hospital and Research Center Oakland, Oakland, California.
authors: Jeffrey D
authors: JD
authors: Merrill
authors: Department of Pediatrics, University of Texas Medical School, Houston, Texas.
authors: Eric C
authors: EC
authors: Eichenwald
authors: Department of Pediatrics, Children's Mercy Hospitals and Clinics, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri.
authors: William E
authors: WE
authors: Truog
authors: Department of Pediatrics, Children's Hospital and Clinics of Minnesota, St. Paul, Minnesota.
authors: Mark C
authors: MC
authors: Mammel
authors: Department of Pediatrics, University of California Davis Children's Hospital, Sacramento, California.
authors: Robin
authors: R
authors: Steinhorn
authors: Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina.
authors: Rita M
authors: RM
authors: Ryan
authors: Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors: Sherry E
authors: SE
authors: Courtney
authors: Department of Pediatrics, University of California, San Francisco, California.
authors: Hart
authors: H
authors: Horneman
authors: Department of Pediatrics, University of California, San Francisco, California.
authors: Roberta A
authors: RA
authors: Ballard
mesh_terms: D000280:Administration, Inhalation; D015415:Biomarkers / Q000652:urine; D001997:Bronchopulmonary Dysplasia / Q000517:prevention & control*; D003404:Creatinine / Q000652:urine; D006152:Cyclic GMP / Q000652:urine*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000517:prevention & control*; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage / Q000652:urine*; D012044:Regression Analysis; D012121:Respiration, Artificial
chemical_list: D015415:Biomarkers; D009569:Nitric Oxide; D003404:Creatinine; D006152:Cyclic GMP