Decreased whole body endogenous nitric oxide production in patients with primary pulmonary hypertension

Impaired pulmonary release of nitric oxide ( NO) is one of the characteristic phenotypic changes of vascular cells in pulmonary hypertension. The aim of this study was to determine nitric oxide synthase (NOS)-dependent whole body NO production in patients with primary pulmonary hypertension. NOS-dependent whole body NO production was assessed by giving an intravenous infusion of L-[N-15](2) -arginine (50 mu mol/min for 30 min) and measuring isotopic urinary enrichment of N-15-nitrite and N-15-nitrate. Four female patients with no signs of infection were recruited and compared with 6 age-matched control subjects. Mean 12-hour excretion of N-15-nitrite and N-15-nitrate in the total urine over 36 h was smaller in patients than in control subjects (57.2 +/- 27.6 vs. 229.1 +/- 65.2 nmol/mmol creatinine, p < 0.01, Mann-Whitney U test, respectively). Neither mean 12-hour excretion of N-14-nitrite and N-14-nitrate (51.6 +/- 10.0 vs. 72.4 +/- 10.0 mu mol/mmol creatinine, p = 0.3) nor glomerular filtration rates (84.5 +/- 15.8 vs. 129.7 +/- 16.0 ml/min, p = 0.1) were different between patients and control subjects. Our results suggest that either basal NOS-dependent whole body NO production is impaired or excess NO metabolism occurs in patients with primary pulmonary hypertension. Copyright (C) 2005 S. Karger AG, Basel.