The effect of ascorbic acid on β-adrenergic-mediated bronchodilator responses in the presence of endogenous nitric oxide

The role played by the interaction of nitric oxide (NO) and endothelins (ET) in the modulation of airway function, and the modulation of β-adrenergic-mediated bronchodilator responses by ascorbic acid in the presence or absence of endogenous NO induced by ET in anesthetized guinea-pigs was examined. Endothelins induced a concentration-dependent increase in respiratory resistance, and pretreatment with the NO synthase inhibitor, NG-nitro-L-arginine methylester, (L-NAME), significantly increased ET-mediated bronchoconstriction. In addition, ET-3-mediated bronchoconstriction following pretreatment with L-NAME was reversed by L-arginine. These findings suggest that the response to the administration of ET-3 can be attributed to the release of NO from the guinea-pig airway. Neither inhaled isoproterenol nor salbutamol significantly affected ET-3-mediated bronchoconstriction, but pretreatment with L-NAME markedly enhanced isoproterenol-mediated bronchodilatation. These findings suggest that endogenous NO induced by ET-3 may attenuate isoproterenol-mediated bronchodilator responses. Ascorbic acid, an antioxidant, enhanced isoproterenol-mediated bronchodilator responses following precontraction with ET-3, but pretreatment with L-NAME reduced this effect of ascorbic acid. The findings suggest that ascorbic acid attenuates the effect of endogenous NO on β-adrenergic- mediated bronchodilator response via its antioxidant activity. Since 10− 7mol/L ET-1 does not induce the release of NO from the guinea-pig airway, ascorbic acid cannot enhance isoproterenol-mediated bronchodilator responses. It seems likely that endogenous NO plays an important regulatory role in modulating β-adrenergic-mediated bronchodilator responses in the airway.