Capsaicin Sensitive Afferents Contribute to Acute Airway Edema following Tracheal Instillation of Hydrochloric Acid or Gastric Juice in the Rat

Abstract

The formation of acute edema in the tracheobronchial mucosa following local instillation of hydrochloric acid or gastric juice was studied in rats. Protein extravasation using the Evans blue technique was measured and used to indicate edema formation. A pH dependent Evans blue extravasation was observed whereby pH 2 produced a small, pH 1.5 an intermediate, and pH 1 a pronounced effect. Also, gastric juice (pH 1.3 .+-. 0.1) induced a marked Evans blue extravasation in the tracheobronchial mucosa. Rats which had been pretreated with capsaicin (100 mg/kg s.c.) had a much lower Evans blue extravasation following local instillation of both hydrochloric acid and gastric juice. Thus, the increase in Evans blue content induced by acid at pH 1.5 was abolished while about 50% of the response remained at pH 1. The protein extravasation caused by gastric juice was reduced by about 70% after capsaicin treatment. Terbutaline (73 nmol/kg, iv) or enprophylline (25 .mu.mol/kg, iv) injected intravenously 10 min before, as well as hydrocortisone injected immediately after the intratracheal instillation of gastric juice, did not influence the magnitude of edema formation. Beta-methasone (0.25 mg/kg ip) pretreatment 24 h prior to the gastric juice exposure enhanced tracheal extravasation. In conclusion, acute protein extravasation in the lower airway mucosa induced by hydrochloric acid or gastric juice is mainly dependent on capsaicin sensitive sensory nerves, suggesting that local release of mediators, such as tachykinins, play a key role in this reaction.