Gastroesophageal acid reflux into the airways can trigger asthma attacks. Indeed, citric acid inhalationcauses bronchoconstriction in guinea pigs, but the mechanism of this effect has not been fullyclarified. We investigated the role of tachykinins, bradykinin, and nitric oxide (NO) on the citric acid–induced bronchoconstriction in anesthetized and artificially ventilated guinea pigs. Citric acid inhalation(2–20 breaths) caused a dose-dependent increase in total pulmonary resistance (RL). RLvalue obtainedafter 10 breaths of citric acid inhalation was not significantly different from the value obtainedafter 20 breaths (p50.22). The effect produced by a half-submaximum dose of citric acid (5 breaths)was halved by the bradykinin B2receptor antagonist HOE 140 (0.1mmol?kg21, intravenous) andabolished by the tachykinin NK2receptor antagonist SR 48968 (0.3mmol?kg21, intravenous). Bronchoconstrictioninduced by a submaximum dose of citric acid (10 breaths) was partially reduced bythe administration of HOE 140, SR 48968, or the NK1receptor antagonist CP-99,994 (8mmol?kg21,intravenous) alone and completely abolished by the combination of SR 48968 and CP-99,994. Pretreatmentwith the NO synthase inhibitor,L-NMMA (1 mM, 10 breaths every 5 min for 30 min) increasedin anL-arginine–dependent manner the effect of citric acid inhalation on RL. HOE 140 and CP-99,994 markedly reduced theL-NMMA–potentiated bronchoconstriction to inhaled citric acid. Weconclude that citric acid–induced bronchoconstriction is caused by tachykinin release from sensorynerves, which, in part, is mediated by endogenously released bradykinin. Simultaneous release of NOby citric acid inhalation counteracts tachykinin-mediated bronchoconstriction. Our study suggests apossible implication of these mechanisms in asthma associated with gastroesophageal acid reflux anda potential therapeutic role of tachykinin and bradykinin antagonists.
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|Anno di pubblicazione:||1999|
|Titolo:||Bronchoconstriction induced by citric acid inhalation in guinea pigs: role of tachykinins, bradykinin, and nitric oxide.|
|Autori:||F. L. Ricciardolo; V. Rado; L. M. Fabbri; P. J. Sterk; G. U. Di; P. Geppetti|
|Appare nelle tipologie:||Articolo su rivista|
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