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

¹ Dept of Pharmacology, University Paris V, Paris, France, ² Dept of Experimental Medicine, Faculty of Medicine and Surgery, Naples, Italy, ³ Sanofi Synthelabo Research, Montpellier, France

CORRESPONDENCE: C. Advenier, Université Paris V, UPRES EA220, Pharmacologie, 45, rue des Saints Pères, F-75006, Paris, France. Fax: 33 142863810. E-mail: charles.advenier@wanadoo.fr

Keywords: airways, oesophageal reflux, tachykinins

Received: June 6, 2001
Accepted January 16, 2002

Gastro-oesophageal reflux is a common clinical disorder associated with a variety of respiratory symptoms, including chronic cough and exacerbation of asthma. In this study, the potential role of acid-induced tachykinin release was examined in guinea pigs and rabbits, by examining the effects of the tachykinin NK₁ and NK₃ receptors antagonists (SR 140333 and SR 142801, respectively) (1–10 mg·kg^–1) on plasma protein extravasation induced in airways by hydrochloric acid (HCl) infusion in the oesophagus.

Guinea pigs were anaesthetised with urethane, while rabbits were subject to neuroleptoanalgesia with hypnorm. Airway vascular leakage was evaluated by measuring extravasation of Evans blue dye. All animals were pretreated with atropine (1 mg·kg^–1 i.p.), propranolol (1 mg·kg^–1 i.p.), phosphoramidon (2.5 mg·kg^–1 i.v.) and saline or tachykinin receptor antagonists (1–10 mg·kg^–1 i.p.).

Infusion of 1 N HCl into the oesophagus led to a three- and five-fold increase in plasma extravasation in the main bronchi and trachea, respectively. This increase was largely prevented by the tachykinin NK₁ and NK₃ receptor antagonists SR 140333 and SR 142801 (1–10 mg·kg^–1).

These results suggest that protein extravasation in the airways, as induced by intra-oesophageal HCl infusion, is mainly dependent on the release of tachykinins, and that both NK₁ and NK₃ tachykinin receptors are involved. The results suggest that HCl-induced sensory nerve stimulation may act in the periphery on intermediate neurons and/or ganglia where NK₃ receptors have been shown to play an important role.

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