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-[(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.
Demoncheaux
Eric A G
EA
Division of Clinical Sciences (South), University of Sheffield, Royal Hallamshire Hospital, Sheffield, UK.
Higenbottam
Tim W
TW
Kiely
David G
DG
Wong
Ju-Ming
JM
Wharton
Simon
S
Varcoe
Richard
R
Siddons
Tom
T
Spivey
Alan C
AC
Hall
Keith
K
Gize
Andy P
AP
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
D009566:Nitrates; D009573:Nitrites; D009587:Nitrogen Isotopes; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase