The role of substance P release in the lung with esophageal acid.
To investigate whether tachykinins are released in the airways by stimulating the esophagus, airway plasma extravasation induced by intraesophageal hydrochloric acid (HCl) in the presence or absence of the neutral endopeptidase (NEP) inhibitor phosphoramidon and the neurokinin-1-receptor antagonist FK888 was studied in anesthetized guinea pigs. Airway plasma extravasation also was studied in the presence of the NEP inhibitor in guinea pigs pretreated with capsaicin or bilateral vagotomy. Propranolol and atropine were used in all animals to block adrenergic and cholinergic nerve effects. Airway plasma leakage was evaluated by measuring extravasated Evans blue dye. One normal HCl infusion into the esophagus significantly increased plasma extravasation in the trachea. Phosphoramidon significantly potentiated plasma extravasation induced by HCl infusion into the esophagus in the trachea and main bronchi, and FK888 significantly inhibited extravasation in a dose-related manner. In 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 bilaterally vagotomized animals. These results suggest that locally acting substances are released by intraesophageal HCl stimulation that cause airway plasma extravasation. These substances are generated through activation of neural pathways, including some that traffic through the vagus nerves that link the esophagus or airways.
Kohrogi
H
H
First Department of Internal Medicine, Kumamoto University School of Medicine, 1-1-1 Honjo Kumamoto 860-8556, Japan.
Hamamoto
J
J
Kawano
O
O
Iwagoe
H
H
Fujii
K
K
Hirata
N
N
Ando
M
M
D000818:Animals; D004151:Dipeptides / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004947:Esophagus / Q000187:drug effects*; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000150:complications / Q000188:drug therapy*; D006020:Glycopeptides / Q000494:pharmacology*; D006168:Guinea Pigs; D006851:Hydrochloric Acid / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values; D012680:Sensitivity and Specificity; D013373:Substance P / Q000187:drug effects / Q000378:metabolism*; D014628:Vagotomy
D004151:Dipeptides; D006020:Glycopeptides; D007211:Indoles; C078949:FK 888; D013373:Substance P; D006851:Hydrochloric Acid; C008890:phosphoramidon