Decreased exhaled nitric oxide in pulmonary arterial hypertension: Response to Bosentan therapy

Reda E. Girgis, Hunter C. Champion, Gregory B. Diette, Roger A. Johns, Solbert Permutt, J. T. Sylvester

Research output: Contribution to journalArticle

Abstract

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 (FENO) determined at multiple expiratory flows. Analysis of the relation between FENO and flow allowed derivation of three flow-independent parameters: airway wall concentration (CW), diffusing capacity (DNO), and alveolar concentration (CA). Seven patients underwent follow-up testing after 3 months of bosentan treatment. Results: At baseline, FENO 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). CW 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 μM NOx/mM creatinine versus 62 ± 7 in control subjects; p = 0.04). After bosentan, FENO, CW, and urine NOx increased to control values (p < 0.05). Exclusion of the two anorexigen cases did not alter these results. Conclusions: FENO at low expiratory flows was decreased in PAH due to reduced CW. Bosentan reversed these abnormalities, suggesting that suppression of NO in PAH may have been caused by endothelin.

Original languageEnglish (US)
Pages (from-to)352-357
Number of pages6
JournalAmerican journal of respiratory and critical care medicine
Volume172
Issue number3
DOIs
StatePublished - Aug 1 2005

Keywords

  • Airway
  • Endothelin
  • Urine nitric oxide metabolites

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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