Inhibition of nitric oxide synthase by nasal decongestants

The nasal decongestants oxymetazoline and xylometazoline are frequently use d in the topical treatment of rhinitis and sinusitis. As nitric oxide (NO) is thought to play a role in inflammation of the upper respiratory tract, t he aim of this study was to examine the in vitro effects of these compounds on the activity and the expression of NO producing enzymes, including the inducible form of NO synthase (MOS) and the constitutive isoform of NO synt hase (cNOS), Experiments concerning the effects of both compounds on enzymatic activity and enzyme induction of iNOS were performed in a lipopolysaccharide (LPS) i nduced rat alveolar macrophage cell line (NR8383) using the Griess assay an d the H-3-citrulline assay respectively. The effects on cNOS were examined in fresh rat synaptosomes using the H-3-citrulline assay. The direct scaven ging properties of both compounds were investigated using a amperometric NO sensor. Oxymetazoline and xylometazoline were shown to have a dose dependent inhibi tory effect on total iNOS activity indicated by nitrite/nitrate formation i n the Griess assay. This effect was found to be due to an inhibition of ind uction of the enzyme rather than inhibition of the enzyme activity, as was investigated in two separate experiments using the H-3-citrulline assay. In hibition of cNOS was moderate and in the same order of magnitude as the inh ibition of enzymatic iNOS activity. Direct scavenging of NO could not be de tected. As constitutive nitric oxide synthase activity is thought to serve benefici al physiological functions, and exaggerated inducible nitric oxide synthase activity may cause exacerbation of the inflammatory process, pharmacologic al treatment influencing the nitric oxide generating system should focus on inhibition of inducible nitric oxide synthase alone. The specific characte ristics of these decongestants in vitro suggests suitability for this appli cation and may indicate an additional beneficial effect in the treatment of upper respiratory tract inflammation.