Role of tachykinin and bradykinin receptors and mast cells in gaseous formaldehyde-induced airway microvascular leakage in rats.
We have investigated the effects of CP-99,994 [(+)-(2s,3s)-3-(2-methoxybenzylamino)-2-phenylpiperidine], a tachykinin NK1 receptor antagonist, HOE 140 (D-Arg[Hyp3,Thi5,D-Tic7,Oic8]bradykinin), a bradykinin B2 receptor antagonist, and ketotifen (4-(1-methyl-4-piperidylidene)4 H-benzo[4,5]cycloheptal[1,2-b]thiophen-10(9H)-one hydrogen fumarate), a histamine H1 receptor antagonist with mast cell-stabilizing properties, on microvascular leakage induced by gaseous formaldehyde. Extravasation of Evans blue dye into airway tissues was used as an index of airway microvascular leakage. Leakage of dye in the trachea and main bronchi increased significantly in a concentration-dependent fashion after 10 min inhalation of formaldehyde (5-45 parts per million (ppm)). The airway response induced by 10 min inhalation of 15 ppm formaldehyde (trachea: 119.5 +/- 13.9 ng/mg, n = 7; main bronchi: 139.6 +/- 7.9 ng/mg, n = 7) was abolished by the administration of CP-99,994 (3 and 6 mg/kg i.v.), but not by the administration of HOE 140 (0.65 mg/kg i.v.) nor ketotifen (1 mg/kg i.v.). The increase in vascular permeability induced by formaldehyde in the rat airway was mediated predominantly by NK1 receptor stimulation. Activation of bradykinin receptors and mast cells did not appear to play an important role in this airway response.
Ito
K
K
Department of Pediatrics, Nagoya University School of Medicine, Japan.
Sakamoto
T
T
Hayashi
Y
Y
Morishita
M
M
Shibata
E
E
Sakai
K
K
Takeuchi
Y
Y
Torii
S
S
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D001980:Bronchi / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D019559:Capillary Leak Syndrome / Q000139:chemically induced / Q000503:physiopathology; D002199:Capillary Permeability / Q000187:drug effects*; D005557:Formaldehyde / Q000009:adverse effects*; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D007665:Ketotifen / Q000494:pharmacology*; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043782:Receptor, Bradykinin B2; D013047:Specific Pathogen-Free Organisms; D014132:Trachea / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology
D065168:Bradykinin Receptor Antagonists; D006634:Histamine H1 Antagonists; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D043782:Receptor, Bradykinin B2; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; D005557:Formaldehyde; C065679:icatibant; D001920:Bradykinin; D007665:Ketotifen