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Increasing Pulmonary Artery Pulsatile Flow Improves Hypoxic Pulmonary Hypertension in Piglets
Published on: May 11, 2015
Decreased exhaled nitric oxide in pulmonary arterial hypertension: response to bosentan therapy
Reda E Girgis1, Hunter C Champion, Gregory B Diette
1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA. rgirgis@jhmi.edu
Rationale:
Decreased nitric oxide (NO) is considered an important pathogenetic mechanism in pulmonary arterial hypertension (PAH), but clear evidence is lacking.
Objectives:
We used multiple techniques to assess endogenous NO in 10 patients with untreated PAH (8 idiopathic and 2 anorexigen-associated PAH) and 12 control subjects.
Methods:
After a nitrite/nitrate-restricted diet, NO metabolites (NOx) were assayed in 24-hour urine collections and exhaled NO (FE(NO)) determined at multiple expiratory flows. Analysis of the relation between FE(NO) and flow allowed derivation of three flow-independent parameters: airway wall concentration (C(W)), diffusing capacity (D(NO)), and alveolar concentration (C(A)). Seven patients underwent follow-up testing after 3 months of bosentan treatment.
Results:
At baseline, FE(NO) was markedly decreased at the two lowest expiratory flows in PAH: 21 +/- 4 versus 36 +/- 4 ppb at 18 ml/second and 11 +/- 2 versus 17 +/- 2 ppb at 50 ml/second, for subjects with PAH and control subjects, respectively (p < 0.05). C(W) was 33 +/- 11 ppb in subjects with PAH versus 104 +/- 34 in control subjects (p = 0.04). Urinary NOx was also reduced in PAH (42 +/- 6 microM NOx/mM creatinine versus 62 +/- 7 in control subjects; p = 0.04). After bosentan, FE(NO), C(W), and urine NOx increased to control values (p < 0.05). Exclusion of the two anorexigen cases did not alter these results.
Conclusions:
FE(NO) at low expiratory flows was decreased in PAH due to reduced C(W). Bosentan reversed these abnormalities, suggesting that suppression of NO in PAH may have been caused by endothelin.
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