Time course for urinary nitric oxide metabolites (NOx) and cyclic guanosine monophosphate (cGMP) in inhaled nitric oxide (iNO)-treated infants. (A) Example of the time course for one infant by days in the study and iNO dose: 24 weeks’ gestation, 640 g birth-weight infant who was enrolled on postnatal day 7. (B) Summary of levels by iNO dose. Data are mean ± standard error (SE) for 2 to 5 values for 102 to 120 iNO-treated infants at each dose and mean ± SE for 120 samples from 19 control infants over the same age range. For iNO-treated infants, all values for NOx are significantly different (p < 0.01) from each other, the cGMP level at 10 to 20 ppm is greater than at other doses (p < 0.001), and cGMP/NOx off iNO is greater than at all iNO doses (p < 0.001). Creatinine levels (not shown) increased with postnatal age (mean ± SD, 12.6 ± 7.5, slope = 0.13 mg/dL/d, r = 0.22, p < 0.001). (C) Regression plots of NOx and cGMP values by iNO dose. Parallel slopes are observed with maximal increase for NOx and cGMP of 3.1-fold and 2-fold, respectively; on linear regression, p for slope is 0.02 for both parameters. Data from part (B).