Am. J. Respir. Crit. Care Med., Volume 158, Number 5, November 1998, 1374-1378

Prostaglandins E₂ and F₂ Reduce Exhaled Nitric Oxide in Normal and Asthmatic Subjects Irrespective of Airway Caliber Changes

SERGEI A. KHARITONOV, MARIA A. SAPIENZA, PETER J. BARNES, and K. FAN CHUNG

Department of Thoracic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London, United Kingdom

Cyclooxygenase products modulate the expression of nitric oxide synthase (NOS) in certain cell types. We determined the effect of prostaglandins (PG) E₂ and F₂ on exhaled nitric oxide (NO) concentrations measured by chemiluminescence. Inhaled PGE₂ and PGF₂ significantly reduced exhaled NO. After the highest dose of PGE₂ (100 µg), NO concentrations fell from 6.9 ± 0.5 ppb to 4.0 ± 0.8 ppb (p < 0.001), and from 22.9 ± 2.0 ppb to 12.3 ± 1.2 ppb (p < 0.001), whereas after PGF₂, it fell from 6.5 ± 0.6 ppb to 3.0 ± 0.5 ppb (p < 0.001), and from 26.0 ± 3.4 ppb to 11.5 ± 1.4 ppb (p < 0.001) in normal (n = 7) and asthmatic (n = 8) subjects, respectively. Although the prostaglandins did not change FEV₁ in normal subjects, PGE₂ caused an increase in asthmatics (from 3.6 ± 0.3 L to 3.8 ± 0.4 L, p < 0.05) and PGF₂ caused a transient reduction in FEV₁ from 4.0 ± 0.2 L to 3.5 ± 0.2 L (p < 0.05). To further determine the relationship between bronchoconstriction and exhaled NO levels, we examined the effect of inhaled methacholine which did not change exhaled NO concentrations in normal and asthmatic subjects despite a greater than 20% fall in FEV₁ in asthmatics. Therefore, PGE₂ and PGF₂ reduce exhaled NO, an effect not related to airway caliber changes but which may result from an inhibition of nitric oxide synthase (NOS), particularly inducible NOS (iNOS).

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