Esophageal stimulation by hydrochloric acid causes neurogenic inflammation in the airways in guinea pigs

Abstract

To investigate whether tachykinins are released in the airways in response to stimulation of the esophagus, we studied the airway plasma extravasation induced by intraesophageal HCl in the presence or absence of neutral endopeptidase inhibitor phosphoramidon and NK1-receptor antagonist FK-888 in anesthetized guinea pigs. The airway plasma leakage was evaluated by measuring extravasated Evans blue dye in the animals pretreated with propranolol and atropine. Infusion of 1 N HCl into the esophagus significantly increased plasma extravasation in the trachea. Phosphoramidon significantly potentiated plasma extravasation in the trachea and main bronchi, whereas FK-888 significantly inhibited that extravasation in a dose-related manner. In the capsaicin-treated animals, airway plasma extravasation was completely inhibited even in the presence of phosphoramidon. Tracheal plasma extravasation potentiated by phosphoramidon was significantly inhibited in the bilateral vagotomized animals. These results suggest that 1) tachykinin-like substances are released to cause plasma extravasation in the airways as a result of intraesophageal HCl stimulation and 2) there are neural pathways communicating between the esophagus and airways, including the vagus nerve.

Tachykinins and airway microvascular leakage induced by HCl intra-oesophageal instillation

“…Airway plasma extravasation was abolished by capsaicin in rabbits, in agreement with previous results obtained in guinea pigs by HAMAMOTO et al [12]. These authors also demonstrated that this effect was inhibited in the guinea pig by the tachykinin NK 1 receptor antagonist, FK 888.…”

“…This effect is abolished in animals treated with capsaicin, a drug that induces a depletion of tachykinins from sensory nerves, or by the tachykinin NK 1 receptor antagonist FK 888. As these effects were observed in animals pretreated with atropine and propranolol and were abolished by bilateral vagotomy, HAMAMOTO et al [12] suggested that HCl effects in that airway involve nerve pathways in the periphery.…”

“…HAMAMOTO et al [12] have shown that HCl infusion in guinea-pig oesophagus causes plasma extravasation in the airways. This effect is abolished in animals treated with capsaicin, a drug that induces a depletion of tachykinins from sensory nerves, or by the tachykinin NK 1 receptor antagonist FK 888.…”

“…However, the involvement of C-fibres and tachykinins has recently been reported in a model of airway neurogenic inflammation, induced by intra-oesophageal HCl stimulation in guinea pigs [12].…”

Recombinant DNase in cystic fibrosis: a protocol for targeted introduction through n-of-1 trials

“…The concept of acid stimulation of distal oesophageal receptors activating an oesophageal±tracheobronchial reflex has gained wider support [29]. The lung and the gut, having a common embryological origin, share a similar neural supply, the vagus nerve, and recent studies have described neurogenic inflammation in the lungs of guinea-pigs after instillation of acid into the distal oesophagus [30]. Biopsy of skin after calcitonin gene-related peptide injection reveals an eosinophilic infiltration [31] and it is recognized that substance P has a degranulating effect on eosinophils [32].…”