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

Allergology International

关键词: antioxidant;    β-adrenergic function;    endothelin;    guinea-pig airway;    nitric oxide;   

DOI  :  10.2332/allergolint.45.55

来源: DOAJ

【 摘 要 】

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 10-7 mol/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.

【 授权许可】

Unknown