[en] The pharmacological mechanisms involved in the substance P (SP)-induced pulmonary oedema were studied in isolated perfused rabbit lungs. Substance P induced a dose-dependent increase in the capillary filtration coefficient (Kf,c), responsible for oedema. Atropine, hemicholinium-3 and ruthenium red pretreatment partly protected the lungs against SP effects, while tetrodotoxin and hexamethonium did not significantly modify them. (+/-)CP96,345, a NK1 receptor antagonist, completely inhibited the SP-induced increase in the Kf,c. Like SP, acetylcholine (ACh) and capsaicin also increased the Kf,c. Atropine and (+/-)CP96,345 completely blocked the oedema induced by both drugs. Tetrodotoxin and ruthenium red strongly inhibited the response to capsaicin and acetylcholine. It was concluded that SP-induced pulmonary oedema is in part mediated by a stimulating action on cholinergic efferent nerves, with subsequent release of endogenous acetylcholine. Acetylcholine can, in turn, stimulate the release of SP from excitatory non adrenergic, non cholinergic nerves. The effects induced by capsaicin and exogenous acetylcholine, thus endogenous SP, involve tetrodotoxin-sensitive mechanisms, while those produced by exogenous SP are tetrodotoxin-resistant.
Disciplines :
Veterinary medicine & animal health Pharmacy, pharmacology & toxicology
Author, co-author :
Delaunois, Annie ; Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Biologie et génétique moléculaire
Gustin, Pascal ; Université de Liège - ULiège > Département de sciences fonctionnelles > Pharmacologie, pharmacothérapie et toxicologie
Ansay, Michel ; Université de Liège - ULiège > Services généraux (Faculté de médecine vétérinaire) > Relations académiques et scientifiques (Méd. vétérinaire)
Language :
English
Title :
Mechanisms of substance P-induced pulmonary oedema in the rabbit: interactions between parasympathetic and excitatory NANC nerves.
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