Inhibition of nitric oxide synthase by nasal decongestants

Abstract

The nasal decongestants oxymetazoline and xylometazoline are frequently used 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, the 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 (iNOS) and the constitutive isoform of NO synthase (cNOS).Experiments concerning the effects of both compounds on enzymatic activity and enzyme induction of iNOS were performed in a lipopolysaccharide (LPS) induced rat alveolar macrophage cell line (NR8383) using the Griess assay and the 3 H-citrulline assay respectively. The effects on cNOS were examined in fresh rat synaptosomes using the 3 H-citrulline assay. The direct scavenging properties of both compounds were investigated using a amperometric NO sensor.Oxymetazoline and xylometazoline were shown to have a dose dependent inhibitory effect on total iNOS activity indicated by nitrite/nitrate formation in the Griess assay. This effect was found to be due to an inhibition of induction of the enzyme rather than inhibition of the enzyme activity, as was investigated in two separate experiments using the 3 H-citrulline assay. Inhibition of cNOS was moderate and in the same order of magnitude as the inhibition of enzymatic iNOS activity. Direct scavenging of NO could not be detected.As constitutive nitric oxide synthase activity is thought to serve beneficial physiological functions, and exaggerated inducible nitric oxide synthase activity may cause exacerbation of the inflammatory process, pharmacological treatment influencing the nitric oxide generating system should focus on inhibition of inducible nitric oxide synthase alone. The specific characteristics of these decongestants in vitro suggests suitability for this application and may indicate an additional beneficial effect in the treatment of upper respiratory tract inflammation. Eur Respir J 2000; 16: 437±444.

Oxymetazoline adds to the effectiveness of fluticasone furoate in the treatment of perennial allergic rhinitis

“…In addition to being an a-agonist, oxymetazoline has been shown to have various antioxidative and anti-inflammatory properties. [8][9][10][11][12] Whether any of these effects contributed to our results is unknown. The oxymetazoline was dosed once daily at night.…”

Oxymetazoline Inhibits Proinflammatory Reactions: Effect on Arachidonic Acid-Derived Metabolites

“…Furthermore, Westerveld et al (2000) referred that 0.3 mM oxymetazoline inhibited inducible nitric oxide synthase in a cellular system with rat alveolar macrophage cell line NR 8383, whereas the constitutive nitric oxide synthase was not affected. Oxymetazoline was also a potent inhibitor of lipid peroxidation and excellent hydroxyl radical scavenger (Westerveld et al, 1995).…”

“…Bjerknes and Steinsvag (1993) reported that compounds such as oxymetazoline chloride and xylometazoline chloride inhibit human neutrophil functions including actin polymerization, phagocytosis, and oxidative burst. Furthermore, Westerveld et al (2000) showed that oxymetazoline strongly inhibits the expression of the inducible form of nitric oxide synthase and speculated that nasal decongestants might offer a new tool to reduce inflammatory mechanisms. Westerveld et al (1995) also referred to antioxidant actions of oxymetazoline by showing that this compound is a potent inhibitor of microsomal lipid peroxidation and an excellent hydroxyl radical scavenger.…”

To Study the Utilization Pattern of Nasal Decongestants and their Effects on Heart Rate and Blood Pressure

“…Westerveld et al have also reported that NDs have dose-dependent inhibitory action on total iNOS activity which appears to be beneficial because inducible NO synthase activity may exacerbate the inflammatory process. 13 They also reported that NDs in vitro appear to have additional benefit in the treatment of upper respiratory tract infection.…”