Prostaglandins E2 and F2α reduce exhaled nitric oxide in normal and asthmatic subjects irrespective of airway caliber changes

Cyclooxygenase products modulate the expression of nitric oxide synthase (NOS) in certain cell types. We determined the effect of prostaglandins (PC) E-2 and F-2 alpha on exhaled nitric oxide (NO) concentrations measured by chemiluminescence. Inhaled PCE2 and PCF2 alpha significantly reduced exhaled NO. After the highest dose of PGE(2) (100 mu g), 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 PCF2 alpha, 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, PCE2 caused an increase in asthmatics (from 3.6 +/- 0.3 L to 3.8 +/- 0.4 L, p < 0.05) and PCF2 alpha 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, PGE(2) and PCF2 alpha 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). .