title: Decreased whole body endogenous nitric oxide production in patients with primary pulmonary hypertension.
abstract: 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-[(15)N](2)-arginine (50 micromol/min for 30 min) and measuring isotopic urinary enrichment of (15)N-nitrite and (15)N-nitrate. Four female patients with no signs of infection were recruited and compared with 6 age-matched control subjects. Mean 12-hour excretion of (15)N-nitrite and (15)N-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 (14)N-nitrite and (14)N-nitrate (51.6 +/- 10.0 vs. 72.4 +/- 10.0 micromol/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.
authors.affiliation: Division of Clinical Sciences (South), University of Sheffield, Royal Hallamshire Hospital, Sheffield, UK.
authors.forename: Eric A G
authors.initials: EA
authors.lastname: Demoncheaux
authors.forename: Tim W
authors.initials: TW
authors.lastname: Higenbottam
authors.forename: David G
authors.initials: DG
authors.lastname: Kiely
authors.forename: Ju-Ming
authors.initials: JM
authors.lastname: Wong
authors.forename: Simon
authors.initials: S
authors.lastname: Wharton
authors.forename: Richard
authors.initials: R
authors.lastname: Varcoe
authors.forename: Tom
authors.initials: T
authors.lastname: Siddons
authors.forename: Alan C
authors.initials: AC
authors.lastname: Spivey
authors.forename: Keith
authors.initials: K
authors.lastname: Hall
authors.forename: Andy P
authors.initials: AP
authors.lastname: Gize
mesh_terms: D000328:Adult; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism*; D007275:Injections, Intravenous; D008875:Middle Aged; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009573:Nitrites / Q000652:urine; D009587:Nitrogen Isotopes
chemical_list: D009566:Nitrates; D009573:Nitrites; D009587:Nitrogen Isotopes; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase