The effect of a bradykinin B2 receptor antagonist, NPC-567, on allergen-induced airway responses in a porcine model.
OBJECTIVE
In order to assess the effect of selective blocking of the bradykinin (BK) B2 receptor in allergic airway reactions, the BK B2 receptor antagonist NPC-567 was administered to sensitized pigs before allergen challenge.


METHODS
Fourteen specific pathogen-free pigs sensitized to Ascaris suum were used.


METHODS
NPC-567 (2.5 mg, in 1 ml saline) was delivered as an aerosol twice to six pigs.


METHODS
Ascaris antigen (in 2 ml saline) was given as an aerosol to all pigs and airway mechanics were monitored for 8 h. NPC-567 (2.5 mg) was given at t = -30 min (in 1ml saline) and mixed with the antigen at t = 0 to six pigs.


RESULTS
Allergen challenge caused an acute reaction with a rapid, significant increase in airways resistance from 4.1 +/- 0.5 cm H2O/l/s to a maximum of 16.2 +/- 3.0 cm H2O/l/s in the control pigs. In the NPC-567-treated pigs, the resistance only increased from 2.9 +/- 0.3 cm H2O/l/s to 6.5 +/- 0.9 cm H2O/l/s (p<0.005 compared to controls). There was also a higher reduction in dynamic lung compliance in the controls than in the treated animals upon allergen challenge. The histamine concentration in urine in the control pigs was markedly elevated after allergen challenge peaking at 15-30 min. This release was inhibited in the NPC-567-treated pigs.


CONCLUSIONS
The BK B2 receptor antagonist NPC-567 seems to be effective in inhibiting the acute response to allergen in the pig airways, possibly due to inhibition of mast cell activation via indirect mechanisms. The late obstructive response was reduced as well, probably as a consequence of the reduced mediator release in the acute reaction.
Sylvin
H
H
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. Helena.Sylvin@labmed.ki.se
van der Ploeg
I
I
Alving
K
K
D000336:Aerosols; D000403:Airway Resistance / Q000187:drug effects; D000485:Allergens / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001200:Ascaris / Q000276:immunology; D001784:Blood Gas Analysis; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D001981:Bronchial Arteries / Q000187:drug effects; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006636:Histamine Release / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D006967:Hypersensitivity / Q000378:metabolism / Q000517:prevention & control; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D043782:Receptor, Bradykinin B2; D012039:Regional Blood Flow / Q000187:drug effects; D015656:Respiratory Mechanics / Q000187:drug effects*; D013552:Swine
D000336:Aerosols; D000485:Allergens; D065168:Bradykinin Receptor Antagonists; D043782:Receptor, Bradykinin B2; C053010:NPC 567; D001920:Bradykinin