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 language | English (US) |
|---|---|
| Pages (from-to) | 352-357 |
| Number of pages | 6 |
| Journal | American Journal of Respiratory and Critical Care Medicine |
| Volume | 172 |
| Issue number | 3 |
| DOIs | |
| State | Published - Aug 1 2005 |
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Keywords
- Airway
- Endothelin
- Urine nitric oxide metabolites
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
Cite this
Decreased exhaled nitric oxide in pulmonary arterial hypertension : Response to Bosentan therapy. / Girgis, Reda E.; Champion, Hunter C.; Diette, Gregory B; Johns, Roger A; Permutt, Solbert; Sylvester, J. T.
In: American Journal of Respiratory and Critical Care Medicine, Vol. 172, No. 3, 01.08.2005, p. 352-357.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Decreased exhaled nitric oxide in pulmonary arterial hypertension
T2 - Response to Bosentan therapy
AU - Girgis, Reda E.
AU - Champion, Hunter C.
AU - Diette, Gregory B
AU - Johns, Roger A
AU - Permutt, Solbert
AU - Sylvester, J. T.
PY - 2005/8/1
Y1 - 2005/8/1
N2 - 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.
AB - 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.
KW - Airway
KW - Endothelin
KW - Urine nitric oxide metabolites
UR - http://www.scopus.com/inward/record.url?scp=22644439894&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=22644439894&partnerID=8YFLogxK
U2 - 10.1164/rccm.200412-1684OC
DO - 10.1164/rccm.200412-1684OC
M3 - Article
C2 - 15879413
AN - SCOPUS:22644439894
VL - 172
SP - 352
EP - 357
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
SN - 1073-449X
IS - 3
ER -